DENGUE IN CITY...BE AWARE...

APART FROM TUBERCULOSIS AND MALARIA....SOMETHING IS MORE  AROUND YOU.

TRY TO KNOW AND BE AWARE, AND FOLLOW BASIC PREVENTION METHODS.

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IN GENERAL -- ABOUT ANTI-MICROBIAL AGENTS

DENGUE - THE CURRENT PROBLEM

           Dengue is a tropical disease which is caused by dengue virus. Dengue is transmitted by mosquitoes especially with genus Aedes i.e. Aedes aegypti. In very rare cases the disease is life threatening while many a times the symptoms are asymptomatic or only have mild symptoms. As such there is no commercially vaccine.

ABOUT VIRUS :- Dengue fever virus is a RNA type virus belongs to family of Flaviviridae and genus Flavivirus. Transmission of virus is through arthropods i.e. via arbovirus ( arthropod borne virus ). Genome of virus contain about 11,000 nucleotide base which is coding for different types of proteins that are C, prM and E, together comprise the viral particle. Four strains of the virus present in atmosphere are DENV-1/ D-1, DENV-2/ D-2, DENV-3/D-3, DENV-4/ D-4.

TRANSMISSION:- Primarily the virus is transmitted through Aedes aegypti. While other species involved in transmitting the disease are A.scutellaris, A.albopictus, A.polynesiensis. Mosquito bite is generally during day time, particularly in early morning or evening. Humans are primary host. Yet many a times primates are also infected. Usually single bit is enough to contract the disease. Virus transmission is also possible through vertical transmission ( from mother to child ) and during organ transplant.

             Female mosquito takes a blood from a person who infected with dengue fever and then becomes itself infected with the virus. About 8–10 days later, the virus spreads to other tissues including the salivary glands of mosquito and is subsequently present its saliva. With contact with human/primates the virus is released inside the host. The virus seems to have no harmful effect on the mosquito, which remains infected for life. 

             
         Once virus enters the host, it binds to cell lining and enters white blood cells, It reproduces inside the cells while they move throughout the body. The white blood cells respond to virus by producing a number of signaling proteins, such as interferon, which are responsible for many of the general symptoms, such a fever, flu-like symptoms and the severe pains. In severe infection occurs , the virus multiplication inside the body is greatly increased, and many more organs can be affected. Furthermore, dysfunction of the bone marrow leads to reduced numbers of platelets, which are necessary for effective blood clotting; this increases the risk of bleeding, the other major complication of dengue fever.

              Once inside the skin, dengue virus binds to Langerhans cells. (a population of dendritic cells.). The dendritic cell moves to the nearest lymph node. Meanwhile, the virus genome is translated in membrane-bound vesicles on the cell's endoplasmic reticulum. Here cell's protein synthesis apparatus produces new viral proteins that replicate the viral RNA and begin to form viral particles. Immature virus particles are transported to the Golgi apparatus and complete mature particle is formed. Mature new viruses bud on the surface of the infected cell and are released through exocytosis. 

              The incubation period (time between exposure and onset of symptoms) ranges from 3–14 days. And therefore, travelers returns from endemic areas show likely symptoms are unlikely to have dengue. Children often experience symptoms similar to those of the common cold and gastroentritis and, though initial symptoms are generally mild but include high fever. Symptoms ignored in children’s or old people can give rise to severe dengue infection which can be life threatening and thus preliminary precautions has to be taken.

SIGNS AND SYMPTOMS:-

                       The general characteristic symptoms of dengue are sudden-onset fever, headache  muscle and joint pains, and a rash. The alternative name for dengue, "break-bone fever", comes from the associated muscle and joint pains. The course of infection is divided into three phases: febrile, critical, and recovery. Phases are associated with pain headache for  3 to 6 days while may a times vomiting is seen due to abdominal discomfort. Measles like rashes are prominently visible, this symptoms should be confused with measles. The fever itself is classically biphasic in nature, breaking and then returning for one or two days, although there is wide variation in how often this pattern actually happens.

                    In some people, the disease proceeds to a critical phase. During this phase there may be significant fluid accumulation in the chest and abdominal cavity due to increased capillary permeability and leakage. This leads to depletion of fluid from the circulation and decreased blood supply to vital organs. During this phase, organ dysfunction and severe bleeding, typically from the gastrointestinal tract, may occur. Shock (dengue shock syndrome) and hemorrhage (dengue hemorrhagic fever) occur in less than 5% of all cases of dengue, however those who have previously been infected with other serotypes of dengue virus ("secondary infection") are at an increased risk.

 DIAGNOSIS:-

             The diagnosis of dengue is typically made clinically, on the basis of reported symptoms and physical examination; this kind of diagnosis is especially carried in endemic areas. However, early disease can be difficult to differentiate from other viral infections. General diagnosis is based on the findings of fever  nausea and vomiting, rash, generalized pains, low white blood cell count, positive tourniquet test, in someone who lives in anendemic area. The diagnosis should be considered in anyone who develops a fever within two weeks of being in the tropics or subtropics. It can be difficult to distinguish dengue fever and chikungunya, as both the viral infection shares many symptoms and occurs in similar parts of the world to dengue. Often, investigations are performed to exclude other conditions that cause similar symptoms, such as malaria, leptospirosis, viral hemorrhagic fever, typhoid fever,  measles, and influenza.

                The earliest change detectable in laboratory testing is a low white blood cell count, which may then be followed by low platelets and metabolic acidosis. A moderately elevated level of aminotransferase from the liver is commonly associated with low platelets and white blood cells. 

             Dengue fever may be diagnosed by microbiological laboratory testing. This can be done by virus isolation in cell cultures, nucleic acid detection by PCR, viral antigen detection or specific antibodies. Virus isolation and nucleic acid detection are more accurate than antigen detection, but these tests are not widely available due to their greater cost.

             Tests for dengue virus-specific antibodies, types IgG and IgM, can be useful in confirming a diagnosis in the later stages of the infection. Both IgG and IgM are produced after 5–7 days. The highest levels of IgM are detected following a primary infection. After a primary infection the IgG reaches peak levels in the blood after 14–21 days. Both IgG and IgM provide protective immunity to the infecting serotype of the virus.

PREVENTION AND CONTROL:- 

- There are no approved vaccines for the dengue virus. 

-Prevention thus depends on control and protection from the bites of the mosquito that transmits it. 

-Elimination of stagnant water at home, schools and work place to avoid breeding of mosquitoes. 

-Using insect repellents over the exposed parts of the body.Using mosquito screens or nets in non – air-conditioned rooms. 

-Wearing the long sleeved clothes like long trousers of a light shade for protection against mosquitoes.

-Properly covering all water tanks so that mosquitoes cannot get in. Getting rid of any container capable of retaining water in the outdoor surroundings (used tyres, food cans, garbage, saucers under flower pots, etc).

- Renew water in flower vases at least once a week. Aedes species is the main target of control. Source reduction of breeding sites of mosquitoe. 

-Requires community involvement to keep the water storage containers free of mosquitoes. Eliminate other breeding places in and around houses. 

-Introduction of larvivorous fish, namely Gambusia and Guppy in water tanks and other water sources. -

-The organophosphorous insecticide ABATE is being used in a large scale. ABATE can prevent breeding upto 3 months when applied to sand granules. It does not affect man or the taste of water. 

-Educate community about the disease, mode of its transmission, availability of treatment and adoption of control measures.

-Changes in practice of storage of water and personal protection should be encouraged. They should also be reassured that this a preventable disease. 

-Community should be advised to cooperate in fogging. Take measures for eliminating breeding places. Special campaigns may be carried out involving mass media including local vernacular newspapers/magazines, radio and TV as well outdoor publicity like hoardings, miking, drum beating, rallies etc. 

-Health education materials should be developed and widely disseminated in the form of posters, pamphlets, handbills. 

-Interpersonal communication through group meetings, traditional/folk media particularly must be optimally utilized.

EPIDEOMOLOGY :-

DIFFERENT CELL WALL STRUCTURE

Gram-Positive Cell Walls

           

  Normally the thick, homogeneous cell wall of gram-positive bacteria is composed primarily of peptidoglycan, which often contains a peptide interbridge. However gram-positive cell walls usually also contain large amounts of teichoic acids, polymers of glycerol or ribitol joined by phosphate groups. Amino acids such as D-alanine or sugars like glucose are attached to the glycerol and ribitol groups.

The teichoic acids are connected to either the peptidoglycan itself by a covalent bond with the six hydroxyl of N-acetylmuramic acid or to plasma membrane lipids; in the latter case they are called lipoteichoic acids. Teichoic acids appear to extend to the surface of the peptidoglycan, and, because they are negatively charged, help give the gram-positive cell wall its negative charge. The functions of these molecules are still unclear, but they may be important in maintaining the structure of the wall. Teichoic acids are not present in gram negative bacteria.

 Gram-Negative Cell Walls

Gram-negative cell walls are much more complex than gram-positive walls. The thin peptidoglycan layer next to the plasma membrane may constitute not more than 5 to 10% of the wall weight. In E. coli it is about 2 nm thick and contains only one or two layers or sheets of peptidoglycan. The outer membrane lies outside the thin peptidoglycan layer. The most abundant membrane protein is Braun’s lipoprotein, a small lipoprotein covalently joined to the underlying peptidoglycan and embedded in the outer membrane by its hydrophobic end. The outer membrane and peptidoglycan are so firmly linked by this 
lipoprotein that they can be isolated as one unit.

Another structure that may strengthen the gram-negative wall and hold the outer membrane in place is the adhesion site. The outer membrane and plasma membrane appear to be in direct contact at many locations in the gram-negative wall. Possibly the most unusual constituents of the outer membrane are its lipopolysaccharides (LPSs). These large, complex molecules contain both lipid and carbohydrate, and consist of three parts: (1) lipid A, (2) the core polysaccharide, and (3) the O side chain. The LPS from Salmonella typhimurium has been studied most, and its general structure is described. The lipid A region contains two glucosamine sugar derivatives, each with three fatty acids and phosphate or pyrophosphate attached. It is buried in the outer membrane and the remainder of the LPS molecule projects from the surface. The core polysaccharide is joined to lipid A. In Salmonella it is constructed of 10 sugars, many of them unusual in structure. The O side chain or O antigen is a polysaccharide chain extending outward from the core. It has several peculiar sugars and varies in composition between bacterial strains.

            LPS has many important functions. As a major constituent of the exterior leaflet of the outer membrane, lipid A also helps in stabilizing outer membrane structure. LPS may contribute to bacterial attachment to surfaces and aids in creating a permeability barrier. LPS restrict the entry of bile salts, antibiotics and other toxic substances. Apart from protecting, LPS is a potent antigen which can elicits an immune response in host e.g. O side chain of LPS.

taken from,

Microbiology book- Prescott, Harley and Klein's Microbiology, McGraw Hill International Edition.

CELL WALL

              The cell wall is the layer, usually fairly rigid, that lies just outside the plasma membrane. Cell wall has many different functions to perform :

1. It helps to determine the shape of the cell, 2. It helps protect the cell from osmotic lysis, 3. It can protect the cell from toxic substances and is the site of action of several antibiotics, 4. In pathogen it can contribute to pathogenicity. Due to all these factors it is important to understand its structure.

             

                After Christian Gram developed the Gram stain in 1884, it soon became evident that bacteria could be divided into two major groups based on their response to the Gram-stain procedure. Gram-positive bacteria stained purple, whereas gram-negative bacteria were colored pink or red by the technique. The true structural difference between these two groups became clear with the advent of the transmission electron microscope. The gram-positive cell wall consists of a single 20 to 80 nm thick homogeneous peptidoglycan  layer lying outside the plasma membrane . Whereas the gram-negative cell wall is quite complex, it has a 2 to 7 nm peptidoglycan layer surrounded by a 7 to 8 nm thick outer membrane. Because of the thicker peptidoglycan layer, the walls of gram-positive cells are stronger than those of gram-negative bacteria. Frequently a space is seen between the plasma membrane and the outer membrane in electron micrographs of gram negative bacteria, and sometimes a similar but smaller gap may be observed between the plasma membrane and wall in gram positive bacteria. This space is called the periplasmic space. The substance that occupies the periplasmic space is the periplasm. The nature of the periplasm space and periplasm differs in gram positive and gram negative bacteria.

Peptidoglycan Structure

 Peptidoglycan or murein is an enormous polymer composed of many identical subunits. The polymer contains two sugar derivatives, N-acetylglucosamine and N-acetylmuramic acid and several different amino acids,—D-glutamic acid, D-alanine, L-alanine and meso-diaminopimelic acid. Three from these amino acids are not found in proteins. The presence of D-amino acids protects against attack by most peptidases. The backbone of this polymer is composed of alternating N-acetylglucosamine and N-acetylmuramic acid residues. A peptide chain of four alternating D- and L-amino acids is connected to the carboxyl group of N-acetylmuramic acid. Many bacteria substitute another diaminoacid, usually L-lysine, in the third position for meso-diaminopimelic acid.  Chains of linked peptidoglycan subunits are joined by crosslinks between the peptides. Often the carboxyl group of the terminal D-alanine is connected directly to the amino group of diaminopimelic acid, but a peptide interbridge may be used instead. This cross-linking results in an enormous peptidoglycan sac that is actually one dense-interconnected network. These sacs have been isolated from gram-positive bacteria and are strong enough to retain their shape and integrity, yet they are elastic and somewhat stretchable, unlike cellulose. They also must be porous, as molecules can penetrate them.

NEW FINGERPRINT LIVES IN YOUR GUT

                A new study is the first to catalog the genetic variation of microbes that lives in the gut, where they extract nutrients from food synthesis vitamins, protect against infections, and produce compounds that are naturally reduce inflammation. The widespread genetic diversity uncovered by the scientists can help them understand how our microbial genes work together with our human genes to keep us healthy or in some cases to cause disease.

               

             The study, by researchers at Washington University School of Medicine in St Louis and the European molecular Biology Laboratory in Heidelberg, Germany, appears online in Nature. “Surprisingly, each of us can be identified by the collective DNA of our gut microbes,” says corresponding author George Weinstock, of Washington University.

           “That collection is individualized, completely analogous to our human genome. Differences in the way individuals respond to various drugs or the way they use specific nutrients can be traced to the genetic variation in our microbial genes as well as in our human genes”

       The researchers analysed the microbial DNA in 252 stool samples from 207 individuals living in the United States and Europe. All the subjects had participated in one of two recent high profile initiatives to catalog the diverse species of microbes that live in and on the body. Neither of those studies – the Human Microbiome Project and the Metagenomics of the Human Intestinal Tract (MetaHIT) project- looked at the genetic variation of the microbial genomes in the body.

          For the new study, the researchers zeroed in on 101 species of microbes commonly found in the intestine, identifying more than 10 million single-letter changes in the collective DNA of those microbes.DNA alterations, including insertions, deletions and structural changes.

           In 43 subjects for whom the researchers had two stool samples collected at least a month apart (most were collected six months to a year after the initial sample), the researchers found very little variability in the microbial DNA over time, although the species of microbes in the intestinal fluctuated.

             “The microbial DNA in the intestine is remarkably stable, like a fingerprint”, Weinstock explains. “Even after a year, we could still distinguish individuals by the genetic signature of their microbial DNA.Babies become colonized with microbes as they pass through the birth canal and into the world. Those microbes come from their mothers and from the environment. Exactly how the microbes shape our lives is not yet known, but in the gut research has suggested that an imbalance of bacteria may contribute to irritable bowel syndrome, Crohn’s and obesity.

              With this new catalog, the researchers can begin to understand the selective forces that shape the microbiome-the collection of microbes and their genes-in the intestine. “The DNA of our microbes is a historical record of the microbial evolution in our bodies”, says co-author Makendonka Mitreva. “Many of these organism would have colonized us when we were very young and would have grown and evolved with us throughout our lifetimes.”

         The information gleaned from future studies of the gut microbiome also may help scientists determine how the microbial genes can be manipulated to improve human health and the effectiveness of certain medications, she adds.