Dengue infection - mechanisms, epidemiology, pathogenesis, diagnosis and management !

DENGUE:

"Dengue is the leading mosquito-borne viral illness infecting humans !"

Dengue is caused by infection with any of the four dengue virus serotypes. This review highlights the mechanisms underlying the clinical course of a dengue infection, which can range from mild febrile illness through to hemorrhagic fever and circulatory shock. It also outlines the epidemiology, pathogenesis, diagnosis and management of dengue infection.

Key phases of dengue infection

Dengue is a mosquito-borne disease caused by infection with dengue virus (DENV). Clinically, the disease can range from a mild febrile illness (previously called dengue fever) through to dengue with warning signs and severe dengue, which includes what were previously called dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS).

 

DENVs belong to the genus Flavivirus of the Flaviviridae family. The four serotypes are enveloped, spherical viral particles with a diameter of approximately 500 Å20. The genome of each serotype comprises approximately 11 kb of positive-sense, single-stranded RNA that encodes ten proteins. The three structural proteins encoded by the genome are the membrane (M) protein, envelope (E) protein and capsid (C) protein; the non-structural (NS) proteins are NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5.

Read More »

CHECK here to download DENGUE RESOURCE eBOOKS

Mechanism how SARS-CoV-2 causes COVID-19 progression !

COVID-19:

"The viral receptor on human cells plays a critical role in disease progression !"

Viruses enter cells and initiate infection by binding to their cognate cell surface receptors. The expression and distribution of viral entry receptors therefore regulates their tropism, determining the tissues that are infected and thus disease pathogenesis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human coronavirus known to co-opt the peptidase angiotensin-converting enzyme 2 (ACE2) for cell entry. The interaction between SARS-CoV-2 and ACE2 is critical to determining both tissue tropism and progression from early SARS-CoV-2 infection to severe coronavirus disease 2019 (COVID-19). Understanding the cellular basis of SARS-CoV-2 infection could reveal treatments that prevent the development of severe disease, and thus reduce mortality.

Key phases of disease progression

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2). Initial infection of cells in the upper respiratory tract may be asymptomatic, but these patients can still transmit the virus. For those who develop symptoms, up to 90% will have pneumonitis, caused by infection of cells in the lower respiratory tract. Some of these patients will progress to severe disease, with disruption of the epithelial-endothelial barrier, and multi-organ involvement.

 

As with all coronaviruses, SARS-CoV-2 cell entry is dependent on its 180-kDa spike (S) protein, which mediates two essential events: binding to ACE2 by the amino-terminal region, and fusion of viral and cellular membranes through the carboxyl-terminal region. Infection of lung cells requires host proteolytic activation of spike at a polybasic furin cleavage site. To date, this cleavage site is found in all spike proteins from clinical SARS-CoV-2 isolates, as well as some other highly pathogenic viruses (e.g., avian influenza A), but it is absent from SARS-CoV and is likely to have been acquired by recombination between coronaviruses in bats. Cleavage by the furin protease therefore expands SARS-CoV-2 cell tropism and may have facilitated transmission from bats to humans. Membrane fusion also requires cleavage by additional proteases, particularly transmembrane protease serine 2 (TMPRSS2), a host cell surface protease that cleaves spike shortly after binding ACE2. SARS-CoV-2 tropism is therefore dependent on expression of cellular proteases, as well as ACE2.

Read More »

         

         

         

DOWNLOAD RESOURCE BOOKS

H2Oh! Water is actually two liquids disguised as one.

H2Oh!

Earth's most precious liquid is weird, and if it wasn't we would die. Now experiments have uncovered its secret: it's not one liquid, it's two

“WATER is very strange,” says Anders Nilsson. He should know: he has been studying the stuff for most of his working life. His claim may be hard for the rest of us to swallow – after all, what could be more ordinary than water? Its behaviour is so familiar, its appearance so commonplace, that we are tricked into assuming that it is more or less the same as everything else. But water is uniquely weird. If it weren’t, none of us would be here to notice.

Lotus Studio/Shutterstock

For example, if water weren’t densest at around 4°C rather than as ice, lakes and rivers would freeze from the bottom up, slowly killing their inhabitants. If it weren’t so spectacularly good at absorbing heat, the planet would have boiled over long ago. And if its molecules, barrelling through membranes or darting down veins, weren’t so good at sweeping other chemicals along, plants and animals would die of malnutrition.

Scientists have been plumbing the depths of water’s strangeness since at least the time of Galileo, to no avail. But now, thanks to the work of Nilsson and others, we might be on the verge of understanding why it behaves the way it does. Their explanation is as strange and wonderful as the stuff itself: water isn’t one liquid, but two.

On one level, it’s no surprise that water comes in multiple forms. It exists in three phases, as a solid, liquid or gas, depending on the temperature and pressure where you find it. At sea level, water turns to steam at 100°C, but at altitude, where the atmospheric pressure is reduced, you can get …

Read More »

Cutaneous Leishmaniasis: Immune Responses in Protection and Pathogenesis.

Immunology

Cutaneous leishmaniasis is a major public health problem and causes a range of diseases from self-healing infections to chronic disfiguring disease. Currently, there is no vaccine for leishmaniasis, and drug therapy is often ineffective. Since the discovery of CD4+ T helper 1 (TH1) cells and TH2 cells 30 years ago, studies of cutaneous leishmaniasis in mice have answered basic immunological questions concerning the development and maintenance of CD4+ T cell subsets. However, new strategies for controlling the human disease have not been forthcoming. Nevertheless, advances in our knowledge of the cells that participate in protection against Leishmania infection and the cells that mediate increased pathology have highlighted new approaches for vaccine development and immunotherapy. In this Review, we discuss the early events associated with infection, the CD4+ T cells that mediate protective immunity and the pathological role that CD8+ T cells can have in cutaneous leishmaniasis.

Cutaneous leishmaniasis — which is caused by several protozoal parasites of the genus Leishmania — is endemic to South and Central America, Northern Africa, the Middle East and parts of Asia, and an estimated 1 million new cases arise each year. Of particular interest to immunologists is the wide range of clinical manifestations associated with this disease, which, similar to tuberculosis and leprosy, is dictated largely by the type and magnitude of the immune response of the host. As in most infections, the immune response to cutaneous leishmaniasis depends on many host factors, as well as on the differences between the infecting Leishmania spp. Experimental infections in mice also exhibit a spectrum of clinical presentations depending on the mouse strain and the infecting parasite species or strain used.

• Cutaneous leishmaniasis exhibits a wide spectrum of clinical presentations that is determined largely by the host immune response. The host immune response to infection is influenced both by host genetics and the Leishmania spp. and/or strain.
• The rapid recruitment of neutrophils and inflammatory monocytes following infection with Leishmania influences the course of disease. Neutrophils can have both protective and deleterious roles, whereas inflammatory monocytes kill Leishmania parasites and differentiate into monocyte-derived dendritic cells that promote the development of protective CD4+ T helper 1 (TH1) cells.
• Control of Leishmania infection depends on the production of interferon-γ by CD4+ TH1 cells, which leads to enhanced killing by macrophages due to the production of reactive oxygen species and nitric oxide.
• CD8+ T cells recruited to Leishmania lesions exhibit a cytolytic profile and lyse infected cells without killing the parasites, which leads to enhanced inflammation and increased severity of disease. Controlling these pathogenic CD8+ T cells, or the downstream mediators of inflammation that they induce, is a new approach to leishmaniasis immunotherapy.
• Infection with Leishmania generates several types of CD4+ T cells that mediate resistance to reinfection, including effector T cells, effector memory T cells, central memory T cells and tissue-resident memory T cells. There is currently no Leishmania vaccine, and a hurdle for vaccine development is that the most effective T cells are short-lived effector T cells; targeting longer lived central memory and tissue-resident memory T cells is an alternative approach.

Read More »