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

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 »

Cracking the Enigma of Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) affects one out of four people in the world, making it the most prevalent of all liver diseases and a major public health problem. The disease is defined by abnormally increased fat deposition in liver cells, which can progress with the addition of inflammation and cell damage to nonalcoholic steatohepatitis (NASH), leading to progressive stages of fibrosis and, finally, cirrhosis. Early NASH is characterized by fat and inflammation associated with minimal amounts of fibrosis, and late NASH is associated with advanced fibrosis or cirrhosis. NAFLD is most closely associated with obesity and diabetes, although there are likely other genetic, nutritional, and environmental factors involved in the pathogenesis.

Although there are no approved pharmacologic treatments for NAFLD, NASH, or cirrhosis, there are over a dozen different companies researching possible treatments. However, the development of drug therapies for the NAFLD spectrum of disease is hampered by a number of challenges:

• the chronic nature of the disorder and ultimately low morbidity and mortality,
• the impact of weight loss on the disease,
• a complex and poorly defined pathophysiology,
• the lack of easily administered diagnostic testing, and
• the evolving status of regulatory endpoints.

Read more: Cracking the Enigma of Fatty Liver Disease

The results of multiple clinical trials over the next few years will clarify potential therapies and target
pathways.  © Sebastian Kaulitzki/Fotolia]

Source: genengnews

Zika Virus — Reigniting The TORCH

The recent association between Zika virus (ZIKV) infection during pregnancy and fetal microcephaly has led to a renewed interest in the mechanisms by which vertically transmitted microorganisms reach the fetus and cause congenital disease. In this Opinion article, we provide an overview of the structure and cellular composition of the human placenta and of the mechanisms by which traditional 'TORCH' pathogens (Toxoplasma gondii, other, rubella virus, cytomegalovirus and herpes simplex virus) access the fetal compartment. Based on our current understanding of ZIKV pathogenesis and the developmental defects that are caused by fetal ZIKV infection, ZIKV should be considered a TORCH pathogen and future research and public health measures should be planned and implemented accordingly.

Zika virus (ZIKV), a member of the Flaviviridae family of RNA viruses, was first isolated in the Zika forest in Uganda in 1947.

Read more: Zika Virus — Reigniting The TORCH

Routes used by TORCH pathogens to overcome the placental barrier. Vertical
transmission and congenital disease induced by ZIKV.

Source: NatureReviewsMicrobiology

Download: Zika Virus — Reigniting The TORCH.pdf

Blood Test Advances Diagnosis Of HELLP Syndrome

A laboratory blood test for the diagnosis of a rare genetic red blood cell disorder also shows promise in identifying HELLP syndrome, a life-threatening high blood pressure condition affecting 1% of all pregnant women.

HELLP is an acronym for hemolysis, elevated liver enzymes and low platelets and is a severe variant of pre-eclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative complement.

Read more: Blood Test Advances Diagnosis Of HELLP Syndrome

A model of the principle underlying the modified Ham test

Source: labmedica