Electrochemical detection of Zika and Dengue infections using a single chip.

Zika and Dengue are infectious diseases caused by flaviviruses and transmitted by Aedes mosquitoes. Although symptoms are usually mild, complications such as dengue hemorrhagic fever and microcephaly in newborns -after the pregnant woman becomes infected with the Zika virus-have emerged as a global public health concern. The co-circulation of Zika and Dengue viruses and the overlapping of their symptoms represent a challenge for the accurate diagnosis. A single test for the point-of-care detection of both diseases is crucial. Here we report a single chip that distinguishes between Zika and Dengue infections using the non-structural protein 1 (NS1) as biomarkers. A novel multiplex electrochemical device containing four independent working electrodes was developed. Zika and Dengue biosensors were fabricated separately on different working electrodes. Selectivity tests showed that the two biosensors can distinguish not only the NS1 proteins from Zika and Dengue but also the spike proteins present in the SARS-CoV-2. This is especially relevant as patients with COVID-19 may have symptoms similar to Zika and Dengue. The gold surface was modified with cysteamine and antibodies against the NS1 proteins. Both biosensors detected their respective biomarkers at clinically relevant concentrations and presented a good linear relationship between the percentage change in impedance and the logarithm of the NS1 concentration (R2 = 0.990 for Dengue and R2 = 0.995 for Zika). Upon combining a simple sample preparation with a portable detection method, our disposable multiplex device offers a point-of-care diagnostic test for Zika and Dengue using a single chip. Additionally, two other biosensors can be added to the chip, providing a platform for viral detection.

The Role of NS1 Protein in the Diagnosis of Flavivirus Infections.

Nonstructural protein 1 (NS1) is a glycoprotein among the flavivirus genus. It is found in both membrane-associated and soluble secreted forms, has an essential role in viral replication, and modulates the host immune response. NS1 is secreted from infected cells within hours after viral infection, and thus immunodetection of NS1 can be used for early serum diagnosis of dengue fever infections instead of real-time (RT)-PCR. This method is fast, simple, and affordable, and its availability could provide an easy point-of-care testing solution for developing countries. Early studies show that detecting NS1 in cerebrospinal fluid (CSF) samples is possible and can improve the surveillance of patients with dengue-associated neurological diseases. NS1 can be detected postmortem in tissue specimens. It can also be identified using noninvasive methods in urine, saliva, and dried blood spots, extending the availability and effective detection period. Recently, an enzyme-linked immunosorbent assay (ELISA) assay for detecting antibodies directed against Zika virus NS1 has been developed and used for diagnosing Zika infection. This NS1-based assay was significantly more specific than envelope protein-based assays, suggesting that similar assays might be more specific for other flaviviruses as well. This review summarizes the knowledge on flaviviruses' NS1's potential role in antigen and antibody diagnosis.

Monitoring human arboviral diseases through wastewater surveillance: Challenges, progress and future opportunities.

Arboviral diseases are caused by a group of viruses spread by the bite of infected arthropods. Amongst these, dengue, Zika, west nile fever and yellow fever cause the greatest economic and social impact. Arboviral epidemics have increased in frequency, magnitude and geographical extent over the past decades and are expected to continue increasing with climate change and expanding urbanisation. Arboviral prevalence is largely underestimated, as most infections are asymptomatic, nevertheless existing surveillance systems are based on passive reporting of loosely defined clinical syndromes with infrequent laboratory confirmation. Wastewater-based surveillance (WBS), which has been demonstrated to be useful for monitoring diseases with significant asymptomatic populations including COVID19 and polio, could be a useful complement to arboviral surveillance. We review the current state of knowledge and identify key factors that affect the feasibility of monitoring arboviral diseases by WBS to include viral shedding loads by infected persons, the persistence of shed arboviruses and the efficiency of their recovery from sewage. We provide a simple model on the volume of wastewater that needs to be processed for detection of arboviruses, in face of lower arboviral shedding rates. In all, this review serves to reflect on the key challenges that need to be addressed and overcome for successful implementation of arboviral WBS.

Near-Infrared Spectroscopy as a Potential COVID-19 Early Detection Method: A Review and Future Perspective.

The coronavirus disease 2019 (COVID-19) pandemic is a worldwide health anxiety. The rapid dispersion of the infection globally results in unparalleled economic, social, and health impacts. The pathogen that causes COVID-19 is known as a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A fast and low-cost diagnosis method for COVID-19 disease can play an important role in controlling its proliferation. Near-infrared spectroscopy (NIRS) is a quick, non-destructive, non-invasive, and inexpensive technique for profiling the chemical and physical structures of a wide range of samples. Furthermore, the NIRS has the advantage of incorporating the internet of things (IoT) application for the effective control and treatment of the disease. In recent years, a significant advancement in instrumentation and spectral analysis methods has resulted in a remarkable impact on the NIRS applications, especially in the medical discipline. To date, NIRS has been applied as a technique for detecting various viruses including zika (ZIKV), chikungunya (CHIKV), influenza, hepatitis C, dengue (DENV), and human immunodeficiency (HIV). This review aims to outline some historical and contemporary applications of NIRS in virology and its merit as a novel diagnostic technique for SARS-CoV-2.

Frequency of exposure to arboviruses and characterization of Guillain Barré syndrome in a clinical cohort of patients treated at a tertiary referral center in Brasília, Federal District.

BACKGROUND: Guillian Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy often associated with previous exposure to infectious agents. METHODS: A clinical cohort of 41 patients with GBS admitted to the Base Hospital Institute of the Federal District between May 2017 and April 2019 was followed up for 1 year. Serological tests for arbovirus detection and amplification of nucleic acids using polymerase chain reaction for zika virus (ZIKV), dengue virus (DENV), and chikungunya virus (CHIKV) were performed. RESULTS: The cohort consisted of 61% men with a median age of 40 years, and 83% had GBS-triggering events. A total of 54% had Grade 4 disability, 17% had Grade 3, 12% had Grade 2, 10% had Grade 5, and 7% had Grade 1. The classic form occurred in 83% of patients. Nerve conduction evaluations revealed acute demyelinating inflammatory polyneuropathy (51%), acute motor axonal neuropathy (17%), acute sensory-motor neuropathy (15%), and indeterminate forms (17%). Four patients were seropositive for DENV. There was no laboratory detection of ZIKV or CHIKV infection. Ninety percent of patients received human immunoglobulin. Intensive care unit admission occurred in 17.1% of the patients, and mechanical ventilation was used in 14.6%. One patient died of Bickerstaff's encephalitis. Most patients showed an improvement in disability at 10 weeks of follow-up. CONCLUSIONS: GBS in the Federal District showed a variable clinical spectrum, and it was possible to detect recent exposure to DENV.

Virus Detection: From State-of-the-Art Laboratories to Smartphone-Based Point-of-Care Testing.

Infectious virus outbreaks pose a significant challenge to public healthcare systems. Early and accurate virus diagnosis is critical to prevent the spread of the virus, especially when no specific vaccine or effective medicine is available. In clinics, the most commonly used viral detection methods are molecular techniques that involve the measurement of nucleic acids or proteins biomarkers. However, most clinic-based methods require complex infrastructure and expensive equipment, which are not suitable for low-resource settings. Over the past years, smartphone-based point-of-care testing (POCT) has rapidly emerged as a potential alternative to laboratory-based clinical diagnosis. This review summarizes the latest development of virus detection. First, laboratory-based and POCT-based viral diagnostic techniques are compared, both of which rely on immunosensing and nucleic acid detection. Then, various smartphone-based POCT diagnostic techniques, including optical biosensors, electrochemical biosensors, and other types of biosensors are discussed. Moreover, this review covers the development of smartphone-based POCT diagnostics for various viruses including COVID-19, Ebola, influenza, Zika, HIV, et al. Finally, the prospects and challenges of smartphone-based POCT diagnostics are discussed. It is believed that this review will aid researchers better understand the current challenges and prospects for achieving the ultimate goal of containing disease-causing viruses worldwide.

The Term Newborn: Congenital Infections.

Maternal pathogens can be transmitted to the fetus resulting in congenital infection with sequelae ranging from asymptomatic infection to severe debilitating disease and still birth. The TORCH pneumonic (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus) is used widely, but it provides a limited description of the expanding list of pathogens associated with congenital infection. This article focuses on the evaluation and management of infants with common congenital infections such as cytomegalovirus, and infections that warrant early diagnosis and treatment to prevent serious complications, such as toxoplasmosis, human immunodeficiency virus, and syphilis. Zika virus and Chagas disease remain uncommon.

Evaluation of Serologic Cross-Reactivity Between Dengue Virus and SARS-CoV-2 in Patients with Acute Febrile Illness - United States and Puerto Rico, April 2020-March 2021.

The diagnosis of dengue disease, caused by the dengue virus (DENV) (a flavivirus), often requires serologic testing during acute and early convalescent phases of the disease. Some symptoms of DENV infection, such as nonspecific fever, are similar to those caused by infection with SARS-CoV-2, the virus that causes COVID-19. In studies with few COVID-19 cases, positive DENV immunoglobulin M (IgM) results were reported with various serologic tests, indicating possible cross-reactivity in these tests for DENV and SARS-CoV-2 infections (1,2). DENV antibodies can cross-react with other flaviviruses, including Zika virus. To assess the potential cross-reactivity of SARS-CoV-2, DENV, and Zika virus IgM antibodies, serum specimens from 97 patients from Puerto Rico and 12 U.S.-based patients with confirmed COVID-19 were tested using the DENV Detect IgM Capture enzyme-linked immunosorbent assay (ELISA) (InBios International).* In addition, 122 serum specimens from patients with confirmed dengue and 121 from patients with confirmed Zika virus disease (all from Puerto Rico) were tested using the SARS-CoV-2 pan-Ig Spike Protein ELISA (CDC).† Results obtained for DENV, Zika virus IgM, and SARS-CoV-2 antibodies indicated 98% test specificity and minimal levels of cross-reactivity between the two flaviviruses and SARS-CoV-2. These findings indicate that diagnoses of dengue or Zika virus diseases with the serological assays described in this report are not affected by COVID-19, nor do dengue or Zika virus diseases interfere with the diagnosis of COVID-19.

Emerging tropical neurological infections.

A large majority of neurological infections remain undiagnosed worldwide. Emerging and re-emerging infections are likely to be responsible for a significant proportion of these. Over the last two decades, several new organisms producing neurological infection and the neurotropic potential of many other known pathogens have been identified. Large outbreaks caused by re-emerging pathogens such as Chikungunya virus, Zika virus and Ebola virus have led to better delineation of their neurological manifestations. Recognition of the pandemic potential of emerging pathogens and an improved understanding of their host-vector-environment interactions would help us be better prepared to meet these emerging threats.

CRISPR Tackles Emerging Viral Pathogens.

Understanding the dynamic relationship between viral pathogens and cellular host factors is critical to furthering our knowledge of viral replication, disease mechanisms and development of anti-viral therapeutics. CRISPR genome editing technology has enhanced this understanding, by allowing identification of pro-viral and anti-viral cellular host factors for a wide range of viruses, most recently the cause of the COVID-19 pandemic, SARS-CoV-2. This review will discuss how CRISPR knockout and CRISPR activation genome-wide screening methods are a robust tool to investigate the viral life cycle and how other class 2 CRISPR systems are being repurposed for diagnostics.

[Viral infections in urology]. / Virusinfektionen in der Urologie.

INTRODUCTION: The COVID (coronavirus disease 2019) pandemic has shown impressively that infectious diseases can have an enormous impact on the healthcare system and beyond. In the specialty of urology, patients present in daily practice with viral infections that are associated with numerous diseases. METHODOLOGY: The aim of this review is to describe viral infections relevant for urology, and in particular to emphasize vaccination prevention. A selective literature search was carried out on the subjects of "COVID and urology", "urogenital viral infections", "viral urological infections in transplant medicine", and "vaccination prevention of viral diseases". RESULTS: Coronaviruses have already caused two local epidemics: SARS (severe acute respiratory syndrome) epidemic and MERS (Middle East respiratory syndrome) epidemic. The fact that the SARS-CoV­2 (SARS coronavirus 2) disease is contagious even without symptoms has essentially led to the rapid spread and global pandemic. A large number of viruses, which can also induce viremia, have been detected in the ejaculate and are thus associated with a possible urogenital infection. These include the mumps virus, Coxsackie viruses or enteroviruses, among others. It has also been shown that a Zika virus infection can also be sexually transmitted via the sperm as a carrier. Viruses therefore also play an important role in reproduction. When performing kidney transplants, urologists are often confronted with viral infections. The most effective weapon against viruses is prevention by vaccination. CONCLUSION: In terms of ethiopathogenesis, the genitourinary tract is most often affected by viruses, in the context of viremia or through reactivation due to immunosuppression. Immunomodulation and vaccination prophylaxis play a leading role in therapy.

Recent advances in biomedical, biosensor and clinical measurement devices for use in humans and the potential application of these technologies for the study of physiology and disease in wild animals.

The goal of achieving enhanced diagnosis and continuous monitoring of human health has led to a vibrant, dynamic and well-funded field of research in medical sensing and biosensor technologies. The field has many sub-disciplines which focus on different aspects of sensor science; engaging engineers, chemists, biochemists and clinicians, often in interdisciplinary teams. The trends which dominate include the efforts to develop effective point of care tests and implantable/wearable technologies for early diagnosis and continuous monitoring. This review will outline the current state of the art in a number of relevant fields, including device engineering, chemistry, nanoscience and biomolecular detection, and suggest how these advances might be employed to develop effective systems for measuring physiology, detecting infection and monitoring biomarker status in wild animals. Special consideration is also given to the emerging threat of antimicrobial resistance and in the light of the current SARS-CoV-2 outbreak, zoonotic infections. Both of these areas involve significant crossover between animal and human health and are therefore well placed to seed technological developments with applicability to both human and animal health and, more generally, the reviewed technologies have significant potential to find use in the measurement of physiology in wild animals. This article is part of the theme issue 'Measuring physiology in free-living animals (Part II)'.

Pregnancy and viral infections: Mechanisms of fetal damage, diagnosis and prevention of neonatal adverse outcomes from cytomegalovirus to SARS-CoV-2 and Zika virus.

Some maternal infections, contracted before or during pregnancy, can be transmitted to the fetus, during gestation (congenital infection), during labor and childbirth (perinatal infection) and through breastfeeding (postnatal infection). The agents responsible for these infections can be viruses, bacteria, protozoa, fungi. Among the viruses most frequently responsible for congenital infections are Cytomegalovirus (CMV), Herpes simplex 1-2, Herpes virus 6, Varicella zoster. Moreover Hepatitis B and C virus, HIV, Parvovirus B19 and non-polio Enteroviruses when contracted during pregnancy may involve the fetus or newborn at birth. Recently, new viruses have emerged, SARS-Cov-2 and Zika virus, of which we do not yet fully know the characteristics and pathogenic power when contracted during pregnancy. Viral infections in pregnancy can damage the fetus (spontaneous abortion, fetal death, intrauterine growth retardation) or the newborn (congenital anomalies, organ diseases with sequelae of different severity). Some risk factors specifically influence the incidence of transmission to the fetus: the timing of the infection in pregnancy, the order of the infection, primary or reinfection or chronic, the duration of membrane rupture, type of delivery, socio-economic conditions and breastfeeding. Frequently infected neonates, symptomatic at birth, have worse outcomes than asymptomatic. Many asymptomatic babies develop long term neurosensory outcomes. The way in which the virus interacts with the maternal immune system, the maternal-fetal interface and the placenta explain these results and also the differences that are observed from time to time in the fetal­neonatal outcomes of maternal infections. The maternal immune system undergoes functional adaptation during pregnancy, once thought as physiological immunosuppression. This adaptation, crucial for generating a balance between maternal immunity and fetus, is necessary to promote and support the pregnancy itself and the growth of the fetus. When this adaptation is upset by the viral infection, the balance is broken, and the infection can spread and lead to the adverse outcomes previously described. In this review we will describe the main viral harmful infections in pregnancy and the potential mechanisms of the damages on the fetus and newborn.

Emerging and Re-emerging Infections in Children: COVID/ MIS-C, Zika, Ebola, Measles, Varicella, Pertussis ... Immunizations.

The role of the emergency provider lies at the forefront of recognition and treatment of novel and re-emerging infectious diseases in children. Familiarity with disease presentations that might be considered rare, such as vaccine-preventable and non-endemic illnesses, is essential in identifying and controlling outbreaks. As we have seen thus far in the novel coronavirus pandemic, susceptibility, severity, transmission, and disease presentation can all have unique patterns in children. Emergency providers also have the potential to play a public health role by using lessons learned from the phenomena of vaccine hesitancy and refusal.

A travel-related infection case associated with triple vector-associated infections: Malaria-Dengue-Zika virus.

As international travels and destinations increase, travel-related infections increase. It is reported that 6-87% of the travellers contract travel-related infection during or after the trip. Vector-associated pathogens comprise a significant percentage of travel-related infections. Apart from the ubiquitous COVID19, threats such as Dengue, Chikungunya and Zika virus and tick-borne agents have emerged or re-emerged in recent years. The fact that these infections are carried with similar vectors and cause similar symptoms makes diagnosis difficult. Herein, a case of travel-associated infection with nonspecific symptoms is presented.

Internet of medical things (IoMT)-integrated biosensors for point-of-care testing of infectious diseases.

On global scale, the current situation of pandemic is symptomatic of increased incidences of contagious diseases caused by pathogens. The faster spread of these diseases, in a moderately short timeframe, is threatening the overall population wellbeing and conceivably the economy. The inadequacy of conventional diagnostic tools in terms of time consuming and complex laboratory-based diagnosis process is a major challenge to medical care. In present era, the development of point-of-care testing (POCT) is in demand for fast detection of infectious diseases along with "on-site" results that are helpful in timely and early action for better treatment. In addition, POCT devices also play a crucial role in preventing the transmission of infectious diseases by offering real-time testing and lab quality microbial diagnosis within minutes. Timely diagnosis and further treatment optimization facilitate the containment of outbreaks of infectious diseases. Presently, efforts are being made to support such POCT by the technological development in the field of internet of medical things (IoMT). The IoMT offers wireless-based operation and connectivity of POCT devices with health expert and medical centre. In this review, the recently developed POC diagnostics integrated or future possibilities of integration with IoMT are discussed with focus on emerging and re-emerging infectious diseases like malaria, dengue fever, influenza A (H1N1), human papilloma virus (HPV), Ebola virus disease (EVD), Zika virus (ZIKV), and coronavirus (COVID-19). The IoMT-assisted POCT systems are capable enough to fill the gap between bioinformatics generation, big rapid analytics, and clinical validation. An optimized IoMT-assisted POCT will be useful in understanding the diseases progression, treatment decision, and evaluation of efficacy of prescribed therapy.

Programmable low-cost DNA-based platform for viral RNA detection.

Detection of viruses is critical for controlling disease spread. Recent emerging viral threats, including Zika virus, Ebola virus, and SARS-CoV-2 responsible for coronavirus disease 2019 (COVID-19) highlight the cost and difficulty in responding rapidly. To address these challenges, we develop a platform for low-cost and rapid detection of viral RNA with DNA nanoswitches that mechanically reconfigure in response to specific viruses. Using Zika virus as a model system, we show nonenzymatic detection of viral RNA with selective and multiplexed detection between related viruses and viral strains. For clinical-level sensitivity in biological fluids, we paired the assay with sample preparation using either RNA extraction or isothermal preamplification. Our assay requires minimal laboratory infrastructure and is adaptable to other viruses, as demonstrated by quickly developing DNA nanoswitches to detect SARS-CoV-2 RNA in saliva. Further development and field implementation will improve our ability to detect emergent viral threats and ultimately limit their impact.