Tackling respiratory infections in the 21st century

Introduction Trends in respiratory infection Resistance to antimicrobials and respiratory infections Use of data for surveillance Influenza prevention and treatment Diagnosis of respiratory infections Current cases of diagnostic platforms How COVID-19 changed its imageReferencesRead more

Introduction

While the early ages of the world were marked by devastating plagues of infectious diseases, with millions dead, the new century boasted of incredible advances in medical science that led to what was eventually called “modern medicine.” Along with better availability of health care and the supply of sanitary facilities, water, and other essential hygiene items, infections became less frequent and their impact was significantly lower.

However, infections remain an important factor contributing to the burden of disease in developing areas of the world, even today. Older infectious conditions refuse to go away, even when new ones emerge.

The main architects of this change include anthropogenic changes in the demographic, climatic and technological profiles of recent years. Invasion of human activity and housing in the habitat of wildlife has increased the risk of spreading viruses, bacteria, fungi, and protozoan infections to humans.

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The subsequent spread of these pathogens is driven by factors such as loss of immunity to specific disease agents, increased aging of the population, the appearance of new strains or new virological features, and change. in the habitat of the guests and vectors of the animals. both for human activity and for climate change.

Air pollution, closely linked to the use of fossil fuels in industry, transportation and electricity generation, among other uses, is another major factor contributing to the risk of respiratory viral infections. This is especially so in the slums and among the marginalized and poor.

Globalization promotes the fastest and most distant spread of pathogens and their vectors to new populations through trade in animals and animal products, human movement, and changing transportation patterns.

Trends in respiratory infections

Lower respiratory tract infections are now the third killer in the world today, aggravated by increased antimicrobial resistance. Post-transplant viral infections with organisms other than cytomegalovirus and Epstein-Barr virus (EBV) that are commonly observed are also being detected more frequently as the medicine progresses.

Respiratory fungal infections are becoming more common, while rare fungal pathogens are being identified in people with severe immunodeficiency for any reason. Tuberculosis has spread more wildly than ever since the onset of drug resistance, and resistance to multiple drugs is an insoluble problem worldwide.

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Co-infection with HIV / TB is another diagnostic puzzle that is very difficult to treat, especially because pediatric and elderly tuberculosis is on the rise. Biological products such as anti-tumor necrosis factor (TNF) -α drugs, used to treat autoimmune diseases, can also cause the reactivation of latent tuberculosis. This disease causes 5,000 deaths a year, or nearly a couple million deaths a year.

Another possibility is an increase in occupational lung disease due to the air circulation of microbes such as influenza, chickenpox, respiratory syncytial virus and hantavirus. Tuberculosis remains the largest occupational infection worldwide, with infection rates rising 5 to 10 times in health care workers and symptomatic tuberculosis up to 5 times higher.

Protozoa and helminths continue to cause lung disease in many regions. The risk can only increase as HIV, solid organ transplants, and immunosuppression predispose to reactivating latent infestations.

Influenza, severe acute respiratory syndrome viruses, and RSV cause the highest proportion of hospitalizations and deaths from respiratory infection. Influenza A has multiple subtypes characterized by different combinations of hemagglutinin and neuraminidase antigens. Influenza viruses are likely to continue to threaten human health in the future.

The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed more than 6 million lives in its sudden and vicious progression in the world in just over two years.

Antimicrobial resistance and respiratory infections

Antimicrobial resistance (AMR), along with genetic modification through recombination, genetic regrouping, or cascading mutations, have caused viruses to cross the species barrier, with a higher risk of pandemic viruses.

A recent study in The Lancet reported that respiratory infections were among the three most closely associated infectious syndromes with severe outcomes due to antimicrobial resistance (AMR). Chest infections attributable to AMR caused more than 400,000 directly associated deaths and 1.5 million indirectly associated deaths.

Use of data for surveillance

A new and extensive assessment of the risk of infectious respiratory disease is urgently needed. The usefulness of global surveillance was demonstrated during the current pandemic of coronavirus disease 2019 (COVID-19).

This monitoring and data collection from integrated sources, including digital surveillance, can yield interesting and fruitful results through new bioinformatics tools. These data are crucial to predicting and preparing for overwhelming waves.

Influenza prevention and treatment

Antigenic drift and occasional antigenic changes threaten human health by producing new variants that evade pre-existing immunity. This means that new vaccines should be developed every year, targeting high-risk groups such as the elderly, pregnant women, children under five, health workers, and people with certain predisposing diseases.

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Research on the production of a universal influenza vaccine or widely neutralizing antibodies is urgently needed, given the suboptimal levels of immunity, its rapid decline with current vaccines, and the delay in the production of a new vaccine after an antigenic change.

Oral medications

Oral influenza drugs such as neuraminidase inhibitor (NAI) oseltamivir, zanamivir, laninamivir and peramivir are used for both treatment and post-exposure prophylaxis. Oral medications for COVID-19 to prevent the progression of mild to severe disease have been shown to be very acceptable and helpful.

Although resistance to oseltamivir is increasing, others are still effective. Baloxavir and favipiravir are also available, the former being an endonuclease inhibitor and the latter a broad-spectrum antiviral. Anti-hemagglutinin and non-NAI antibodies such as pimodivir are also being developed.

Palivizumab anti-RSV monoclonal antibody, created by Astra-Zeneca, is now marketed by Swedish Orphan Biovitrum AB (publ) (Sobi) to protect babies at risk during periods of high incidence. Moderna, who created the second messenger ribonucleic acid (mRNA) vaccine against COVID-19, developed an RSV mRNA vaccine.

Diagnosis of respiratory infections

Simple, quick, and relatively inexpensive diagnostic tests are essential to identify respiratory infections well in advance to prevent serious illness. Recent advances include lab-on-a-chip (LOC) technologies that use microfluidic components with biosensors to perform a complex test with speed and specificity, using small amounts of reagent and sample, at very low costs. These platforms can be used as multiplexed tests for point-of-care testing (POCT).

Along with the use of oral medications at an early stage, POCTs can reduce the number of respiratory infections and the risk of outbreaks and RAM. Newer POCT platforms use smart materials and approaches based on nucleic acid amplification (NAAT) techniques; recognition of virus epitopes by antibodies, aptamers, or cavities combined with optical, electrical, electrochemical, magnetic, or other techniques to produce a detectable signal; and immunological testing for viral detection.

CRISPR-based systems can detect nucleic acid very efficiently, especially with case systems such as SHERLOCK (specific high-sensitivity enzyme reporter release) from Sherlock Biosciences, targeted at SARS-CoV-2.

Other POCT devices use non-molecular methods, such as nanoparticles, to detect biomolecules in real time with very high sensitivity and a short response time. Immunofluorescence assays are also used, as well as enzyme-linked immunosorbent assays (ELISAs), protein matrices, and photon excitation assays.

Biosensors provide fast, portable, and sensitive miniaturized platforms for the detection of antigens or antibodies. Surface plasmon resonance (SPR) uses reflectance based on the bonding of the biomolecule-metal surface to detect specific targets. Hybrid nanobiomolecules or transistor-coupled DNA probes are other approaches

Genome-wide sequencing (WGS) using high-performance portable platforms and next-generation sequencing (NGS) technologies also provide fast and efficient viral detection. Multiplexed LOC systems will test multiple pathogens with one sample, saving time and samples.

Current instances of diagnostic platforms

Examples of such systems include the Alere BinaxNOW® platform (formerly Alere i) Influenza A&B (Abbott, USA), QuickVue® Influenza A + B (Quidel Corporation, USA) and the FILMARRAY Respiratory Panel (bioMérieux, France).

Others include the Nanosphere Verigene® RV + test and the Hologic Gen-Probe Prodesse tests. They are based on PCR technology. Others such as mariPOC® Respi test (ArcDia International Oy Ltd, Finland), BD veritor ™ Influenza A + B, BD veritor ™ RSV (Becton Dickinson, USA) and SD Bioline Influenza Ag (Standard Diagnostics Inc., Korea) are not – NAAT Essays.

Meanwhile, integrated sample preparation and testing systems such as the cobas® Liat® system (Roche …

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