History of Hepatitis C virus

History

In the mid-1970s, Harvey J. Alter, Chief of the Infectious Disease Section in the Department of Transfusion Medicine at the National Institutes of Health, and his research team demonstrated how most post-transfusion hepatitis cases were not due to hepatitis A or B viruses. Despite this discovery, international research efforts to identify the virus, initially called non-A, non-B hepatitis (NANBH), failed for the next decade. In 1987, Michael Houghton, Qui-Lim Choo, and George Kuo at Chiron Corporation, collaborating with Dr. D.W. Bradley at the Centers for Disease Control and Prevention, used a novel molecular cloning approach to identify the unknown organism and develop a diagnostic test. In 1988, the virus was confirmed by Alter by verifying its presence in a panel of NANBH specimens. In April 1989, the discovery of HCV was published in two articles in the journal Science.The discovery led to significant improvements in diagnosis and improved antiviral treatment. In 2000, Drs. Alter and Houghton were honored with the Lasker Award for Clinical Medical Research for "pioneering work leading to the discovery of the virus that causes hepatitis C and the development of screening methods that reduced the risk of blood transfusion-associated hepatitis in the U.S. from 30% in 1970 to virtually zero in 2000."

Chiron filed for several patents on the virus and its diagnosis.A competing patent application by the CDC was dropped in 1990 after Chiron paid $1.9 million to the CDC and $337,500 to Bradley. In 1994, Bradley sued Chiron, seeking to invalidate the patent, have himself included as a coinventor, and receive damages and royalty income. He dropped the suit in 1998 after losing before an appeals court.

Epidemiology

Epidemiology

Prevalence of hepatitis C worldwide in 1999

It is estimated that 130–200 million people, or ~3% of the world's population, are living with chronic hepatitis C.About 3–4 million people are infected per year, and more than 350,000 people die yearly from hepatitis C-related diseases. Rates have increased substantially in the 20th century due to a combination of IDU and intravenous medication or poorly sterilized medical equipment.

Among those chronically infected, the risk of cirrhosis after 20 years varies between studies but has been estimated at ~10%-15% for men and ~1-5% for women. The reason for this difference is not known. Once cirrhosis is established, the rate of developing hepatocellular carcinoma is ~1%-4% per year.

In the United States, about 2% of people have hepatitis C, with about 35,000 to 185,000 new cases a year. Rates have decreased in the Western world since the 1990s due to improved screening of blood before transfusion.Annual deaths from HCV in the United States range from 8,000 to 10,000; expectations are that this mortality rate will increase, as those infected by transfusion before HCV testing become apparent.

Prevalence is higher in some countries in Africa and Asia.Countries with particularly high rates of infection include Egypt (22%), Pakistan (4.8%) and China (3.2%). It is believed that the high prevalence in Egypt is linked to a now-discontinued mass-treatment campaign for schistosomiasis, using improperly sterilized glass syringes.

Hepatitis C virus Prognosis

Prognosis

Responses to treatment vary by HCV C genotype, and is measured by sustained viral response. Sustained response is about 40-50% in people with HCV genotype 1 given 48 weeks of treatment. Sustained response is seen in 70-80% of people with HCV genotypes 2 and 3 with 24 weeks of treatment. Sustained response is about 65% in those with genotype 4 given 48 weeks of treatment. The evidence for treatment in genotype 6 disease is sparse, and the evidence that exists is for 48 weeks of treatment at the same doses as are used for genotype 1 disease.

Hepatitis C virusTreatment

Treatment

HCV induces chronic infection in 50–80% of infected persons. Approximately 40-80% of these clear with treatment. In rare cases, infection can clear without treatment. Those with chronichepatitis C are advised to avoid alcohol and medications toxic to the liver, and to be vaccinated for hepatitis A and hepatitis B. Ultrasound surveillance for hepatocellular carcinoma is recommended in those with accompanying cirrhosis.

Medications

In general, treatment is recommended in those with proven HCV infection liver abnormalities. As of 2010, treatments consists of a combination of pegylated interferon alpha and the antiviral drugribavirin for a period of 24 or 48 weeks, depending on HCV genotype. When combined with ribavirin, pegylated interferon-alpha-2a may be superior to pegylated interferon-alpha-2b, though the evidence is not strong. Improved outcomes are seen in 50–60% of people. Combining either boceprevir or telaprevir with ribavirin and peginterferon alfa improves antiviral response for hepatitis C genotype 1. Adverse effects with treatment are common, with half of people getting flu like symptoms and a third experiencing emotional problems. Treatment during the first six months is more effective than once hepatitis C has become chronic. If someone develops a new infection and it has not cleared after eight to twelve weeks, 24 weeks of pegylated interferon is recommended. In people with thalassemia, ribavirin appears to be useful but increases the need for transfusions.

Alternative medicine

Several alternative therapies are claimed by their proponents to be helpful for hepatitis C including milk thistle, ginseng, and colloidal silver. However, no alternative therapy has been shown to improve outcomes in hepatitis C, and no evidence exists that alternative therapies have any effect on the virus at all.

Hepatitis C Prevention

Prevention

As of 2011, no vaccine protects against contracting hepatitis C. However, a number are under development and some have shown encouraging results. A combination of harm reduction strategies, such as the provision of new needles and syringes and treatment of substance use, decrease the risk of hepatitis C in intravenous drug users by about 75%.The screening of blood donors is important at a national level, as is adhering to universal precautions within healthcare facilities. In countries where there is an insufficient supply of sterile syringes, medications should be given orally rather than via injection (when possible)

Hepatitis C Diagnosis

Diagnosis

Serologic profile of Hepatitis C infection

There are a number of diagnostic tests for hepatitis C including: HCV antibody enzyme immunoassay or ELISA, recombinant immunoblot assay, and quantitative HCV RNA polymerase chain reaction (PCR).HCV RNA can be detected by PCR typically one to two weeks after infection, while antibodies can take substantially longer to form and thus be detected.
Chronic hepatitis C is defined as infection with the hepatitis C virus persisting for more than six months based on the presence of its RNA. Chronic infections are typically asymptomatic during the first few decades, and thus are most commonly discovered following the investigation of elevated liver enzyme levels or during a routine screening of high risk individuals. Testing is not able to distinguish between acute and chronic infections.

Serology

Hepatitis C testing typically begins with blood testing to detect the presence of antibodies to the HCV using an enzyme immunoassay. If this test is positive, a confirmatory test is then performed to verify the immunoassay and to determine the viral load. A recombinant immunoblot assay is used to verify the immunoassay and the viral load is determined by a HCV RNA polymerase chain reaction. If there are no RNA and the immunoblot is positive it means that the person had a previous infection but cleared it either with treatment or spontaneously; if the immunoblot is negative, it means that the immunoassay was wrong. It takes about 6–8 weeks following infection before the immunoassay will test positive. A number of tests are available as point of care testing which means that results are available within 30 minutes.
Liver enzymes are variable during the initial part of the infection and on average begin to rise at seven weeks after infection. Liver enzymes are poorly correlated with disease severity.

Biopsy

Liver biopsies are used to determine the degree of liver damage present; however, there are risks from the procedure. The typical changes seen are lymphocytes within the parenchyma, lymphoid follicles in portal triad, and changes to the bile ducts. There are a number of blood tests available that try to determine the degree of hepatic fibrosis and alleviate the need for biopsy.

Screening

It is believed only 5–50% of those infected in the United States and Canada become aware of their status. Testing is recommended in those at high risk, which includes those with tattoos.Screening is also recommended in those with elevated liver enzymes as this is frequently the only sign of chronic hepatitis. Routine screening is not currently recommended in the United States. However, in 2012, the U.S. Centers for Disease Control and Prevention (CDC) recommended a single screening test for those born between 1945 and 1965

Transmission of Hepatitis C virus

Transmission

Hepatitis C infection in the United States by source

The primary route of transmission in the developed world is intravenous drug use (IDU), while in the developing world the main methods are blood transfusions and unsafe medical procedures.The cause of transmission remains unknown in 20% of cases; however, many of these are believed to be accounted for by IDU.

Intravenous drug use

IDU is a major risk factor for hepatitis C in many parts of the world. Of 77 countries reviewed 25 (including the United States) were found to have prevalences of hepatitis C in the intravenous drug user population of between 60% and 80%. Twelve countries had rates greater than 80%.It is believed that ten million intravenous drug users are infected with hepatitis C; China (1.6 million), the United States (1.5 million), and Russia (1.3 million) have the highest absolute totals. Occurrence of hepatitis C among prison inmates in the United States is 10 to 20 times that of the occurrence observed in the general population; this has been attributed to high-risk behavior in prisons such as IDU and tattooing with nonsterile equipment.

Healthcare exposure

Blood transfusion, transfusion of blood products, or organ transplantation without HCV screening carry significant risks of infection. The United States instituted universal screening in 1992and Canada instituted universal screening in 1990. This decreased the risk from one in 200 units to between one in 10,000 to one in 10,000,000 per unit of blood. This low risk remains as there is a period of about 11–70 days between the potential blood donor acquiring hepatitis C and their blood testing positive depending on the method.Some countries do not screen for hepatitis C due to the cost.

Those who have experienced a needle stick injury from someone who was HCV positive have about a 1.8% chance of subsequently contracting the disease themselves. The risk is greater if the needle in question is hollow and the puncture wound is deep. There is a risk from mucosal exposures to blood; but this risk is low, and there is no risk if blood exposure occurs on intact skin.

Hospital equipment has also been documented as a method of transmission of hepatitis C including: reuse of needles and syringes, multiple-use medication vials, infusion bags, and improperly sterilized surgical equipment, among others. Limitations in the implementation and enforcement of stringent standard precautions in public and private medical and dental facilities are known to be the primary cause of the spread of HCV in Egypt, the country with highest rate of infection in the world.

Sexual intercourse

Whether hepatitis C can be transmitted through sexual activity is controversial.While there is an association between high-risk sexual activity and hepatitis C, it is not known whether transmission of the disease is due to drug use that has not been admitted to or sex as a risk factor. The majority of evidence supports there being no risk for monogamous heterosexual couples.Sexual practices that involve higher levels of trauma to the anogenital mucosa, such as anal penetrative sex, or that occur when there is a concurrent sexually transmitted infection, including HIV or genital ulceration, do present a risk. The United States government only recommends condom use to prevent hepatitis C transmission in those with multiple partners.

Body modification

Tattooing is associated with two to threefold increased risk of hepatitis C. This can be due to either improperly sterilized equipment or contamination of the dyes being used. Tattoos or piercings performed either before the mid-1980s, "underground," or nonprofessionally are of particular concern, since sterile techniques in such settings may be lacking. The risk also appears to be greater for larger tattoos. It is estimated that nearly half of prison inmates share unsterilized tattooing equipment.It is rare for tattoos in a licensed facility to be directly associated with HCV infection.

Shared personal items

Personal-care items such as razors, toothbrushes, and manicuring or pedicuring equipment can be contaminated with blood. Sharing such items can potentially lead to exposure to HCV. Appropriate caution should be taken regarding any medical condition that results in bleeding, such as cuts and sores.HCV is not spread through casual contact, such as hugging, kissing, or sharing eating or cooking utensils.Neither is it transmitted through food or water.

Vertical transmission

Vertical transmission of hepatitis C from an infected mother to her child occurs in less than 10% of pregnancies. There are no measures that alter this risk. It is not clear when during pregnancy transmission occurs, but it may occur both during gestation and at delivery. A long labor is associated with a greater risk of transmission. There is no evidence that breast-feeding spreads HCV; however, to be cautious, an infected mother is advised to avoid breastfeeding if her nipples are cracked and bleeding, or her viral loads are high.

please take care

Hepatitis C Virology

Virology

The hepatitis C virus (HCV) is a small, enveloped, single-stranded, positive-sense RNA virus. It is a member of the hepacivirus genus in the family Flaviviridae. There are seven major genotypes of HCV, which are indicated numerically from one to seven. In the United States, about 70% of cases are caused by genotype 1, 20% by genotype 2, and about 1% by each of the other genotypes. Genotype 1 is also the most common in South America and Europe.

Signs and symptoms of Hepatitis C virus

Signs and symptoms

Acute infection

Hepatitis C infection causes acute symptoms in 15% of cases. Symptoms are generally mild and vague, including a decreased appetite, fatigue, nausea, muscle or joint pains, and weight loss and rarely does acute liver failure result. Most cases of acute infection are not associated with jaundice. The infection resolves spontaneously in 10-50% of cases, which occurs more frequently in individuals who are young and female.

Chronic infection

About 80% of those exposed to the virus develop a chronic infection. Most experience minimal or no symptoms during the initial few decades of the infection, although chronic hepatitis C can be associated with fatigue. Hepatitis C after many years becomes the primary cause of cirrhosis and liver cancer. About 10–30% of people develop cirrhosis over 30 years. Cirrhosis is more common in those co-infected with hepatitis B or HIV, alcoholics, and those of male gender.Those who develop cirrhosis have a 20-fold greater risk of hepatocellular carcinoma, a rate of 1–3% per year, and if this is complicated by excess alcohol the risk becomes 100 fold greater. Hepatitis C is the cause of 27% of cirrhosis cases and 25% of hepatocellular carcinoma worldwide.

Liver cirrhosis may lead to portal hypertension, ascites (accumulation of fluid in the abdomen), easy bruising or bleeding, varices (enlarged veins, especially in the stomach and esophagus), jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy. It is a common cause for requiring a liver transplant.

Extrahepatic

Hepatitis C is also rarely associated with Sjögren's syndrome (an autoimmune disorder), thrombocytopenia, lichen planus, diabetes mellitus, and B-cell lymphoproliferative disorders.Thrombocytopenia is estimated to occur in 0.16% to 45.4% of people with chronic hepatitis C. Putative associations with Hyde's prurigo nodularis  and membranoproliferative glomerulonephritis have been reported. Hepatitis C infection is also associated with a condition called mixed cryoglobulinemia, which is inflammation of small and medium sized blood vessels (or vasculitis) caused by deposition of immune complexes involving cryoglobulins.

Hepatitis C virus in General

Hepatitis C

Hepatitis C is an infectious disease affecting primarily the liver, caused by the hepatitis C virus (HCV).The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years. In some cases, those with cirrhosis will go on to develop liver failure, liver cancer or life-threatening esophageal and gastric varices.

HCV is spread primarily by blood-to-blood contact associated with intravenous drug use, poorly sterilized medical equipment and transfusions. An estimated 130–200 million people worldwide are infected with hepatitis C. The existence of hepatitis C (originally "non-A non-B hepatitis") was postulated in the 1970s and proven in 1989. Hepatitis C only infects humans and chimpanzees.

The virus persists in the liver in about 85% of those infected. This persistent infection can be treated with medication: the standard therapy is a combination of peginterferon and ribavirin, with either boceprevir or telaprevir added in some cases. Overall, 50–80% of people treated are cured. Those who develop cirrhosis or liver cancer may require a liver transplant. Hepatitis C is the leading cause of liver transplantation, though the virus usually recurs after transplantation. No vaccine against hepatitis C is available

Modern Microbiology

Modern

Anton van Leeuwenhoek, is considered to be the one of the first to observe microorganisms using a microscope.

In 1676, Anton van Leeuwenhoek observed bacteria and other microorganisms, using a single-lens microscope of his own design. While Van Leeuwenhoek is often cited as the first to observe microbes, Robert Hooke made the first recorded microscopic observation, of the fruiting bodies of molds, in 1665.The first observation of microbes using a microscope is generally credited to the Dutch draper and haberdasher, Antonie van Leeuwenhoek, who lived for most of his life in Delft, Holland. It has, however, been suggested that a Jesuit priest called Athanasius Kircher was the first to observe micro-organisms. He was among the first to design magic lanterns for projection purposes, so he must have been well acquainted with the properties of lenses. One of his books contains a chapter in Latin, which reads in translation – ‘Concerning the wonderful structure of things in nature, investigated by Microscope. Here, he wrote ‘who would believe that vinegar and milk abound with an innumerable multitude of worms.’ He also noted that putrid material is full of innumerable creeping animalcule. These observations antedate Robert Hooke’s Micrographia by nearly 20 years and were published some 29 years before van Leeuwenhoek saw protozoa and 37 years before he described having seen bacteria.

Innovative laboratory glassware and experimental methods developed by Louis Pasteur and other biologists contributed to the young field of bacteriology in the late 19th century.

The field of bacteriology (later a subdiscipline of microbiology) was founded in the 19th century by Ferdinand Cohn, a botanist whose studies on algae and photosynthetic bacteria led him to describe several bacteria including Bacillus and Beggiatoa. Cohn was also the first to formulate a scheme for the taxonomic classification of bacteria and discover spores. Louis Pasteur and Robert Koch were contemporaries of Cohn’s and are often considered to be the father of microbiology and medical microbiology, respectively.Pasteur is most famous for his series of experiments designed to disprove the then widely held theory of spontaneous generation, thereby solidifying microbiology’s identity as a biological science.Pasteur also designed methods for food preservation (pasteurization) and vaccines against several diseases such as anthrax, fowl cholera and rabies. Koch is best known for his contributions to the germ theory of disease, proving that specific diseases were caused by specific pathogenic micro-organisms. He developed a series of criteria that have become known as the Koch's postulates. Koch was one of the first scientists to focus on the isolation of bacteria in pure culture resulting in his description of several novel bacteria including Mycobacterium tuberculosis, the causative agent of tuberculosis.

While Pasteur and Koch are often considered the founders of microbiology, their work did not accurately reflect the true diversity of the microbial world because of their exclusive focus on micro-organisms having direct medical relevance. It was not until the late 19th century and the work of Martinus Beijerinck and Sergei Winogradsky, the founders of general microbiology (an older term encompassing aspects of microbial physiology, diversity and ecology), that the true breadth of microbiology was revealed.Beijerinck made two major contributions to microbiology: the discovery of viruses and the development of enrichment culture techniques. While his work on the Tobacco Mosaic Virus established the basic principles of virology, it was his development of enrichment culturing that had the most immediate impact on microbiology by allowing for the cultivation of a wide range of microbes with wildly different physiologies. Winogradsky was the first to develop the concept of chemolithotrophy and to thereby reveal the essential role played by micro-organisms in geochemical processes. He was responsible for the first isolation and description of both nitrifying and nitrogen-fixing bacteria.French-Canadian microbiologist Felix d'Herelle co-discovered bacteriophages and was one of the earliest applied microbiologists.

Microbiology Benefits

Benefits

While some fear microbes due to the association of some microbes with various human illnesses, many microbes are also responsible for numerous beneficial processes such as industrial fermentation (e.g. the production of alcohol, vinegar and dairy products), antibiotic production and as vehicles for cloning in more complex organisms such as plants. Scientists have also exploited their knowledge of microbes to produce biotechnologically important enzymes such as Taq polymerase, reporter genes for use in other genetic systems and novel molecular biology techniques such as the yeast two-hybrid system.

Bacteria can be used for the industrial production of amino acids. Corynebacterium glutamicum is one of the most important bacterial species with an annual production of more than two million tons of amino acids, mainly L-glutamate and L-lysine.

A variety of biopolymers, such as polysaccharides, polyesters, and polyamides, are produced by microorganisms. Microorganisms are used for the biotechnological production of biopolymers with tailored properties suitable for high-value medical application such as tissue engineering and drug delivery. Microorganisms are used for the biosynthesis of xanthan, alginate, cellulose, cyanophycin, poly(gamma-glutamic acid), levan, hyaluronic acid, organic acids, oligosaccharides and polysaccharide, and polyhydroxyalkanoates.

Microorganisms are beneficial for microbial biodegradation or bioremediation of domestic, agricultural and industrial wastes and subsurface pollution in soils, sediments and marine environments. The ability of each microorganism to degrade toxic waste depends on the nature of each contaminant. Since sites typically have multiple pollutant types, the most effective approach to microbial biodegradation is to use a mixture of bacterial species and strains, each specific to the biodegradation of one or more types of contaminants.

There is considerable evidence supporting microbial contributions to human and animal health. Some benefit may be be conferred by consuming fermented foods, probiotics (bacteria potentially beneficial to the digestive system) and/or prebiotics (substances consumed to promote the growth of probiotic microorganisms).  The importance of bacteria to human health is only beginning to be investigated, a field that is certain to expand in light of recent discoveries that, in humans, bacterial cells outnumber somatic cells by a factor of 10 to one.

Recent research has suggested that microorganisms could be useful in the treatment of cancer. Various strains of non-pathogenic clostridia can infiltrate and replicate within solid tumors. Clostridial vectors can be safely administered and their potential to deliver therapeutic proteins has been demonstrated in a variety of preclinical models.

Microbiology Branches

Branches

The branches of microbiology can be classified into pure and applied sciences. Microbiology can be also classified based on taxonomy, in the cases of bacteriology, mycology, protozoology, and phycology. There is considerable overlap between the specific branches of microbiology with each other and with other disciplines.

Pure microbiology

Taxonomic arrangement

• Bacteriology: The study of bacteria.
• Mycology: The study of fungi.
• Protozoology: The study of protozoa.
• Phycology (or algology): The study of algae.
• Parasitology: The study of parasites.
• Immunology: The study of the immune system.
• Virology: The study of viruses.
• Nematology:The study of the nematodes

Integrative arrangement

• Microbial cytology: The study of microscopic and submicroscopic details of microorganisms.
• Microbial physiology: The study of how the microbial cell functions biochemically. Includes the study of microbial growth, microbial metabolism and microbial cell structure.
• Microbial ecology: The relationship between microorganisms and their environment.
• Microbial genetics: The study of how genes are organized and regulated in microbes in relation to their cellular functions. Closely related to the field of molecular biology.
• Cellular microbiology: A discipline bridging microbiology and cell biology.
• Evolutionary microbiology: The study of the evolution of microbes. This field can be subdivided into:
  • Microbial taxonomy: The naming and classification of microorganisms.
  • Microbial systematics: The study of the diversity and genetic relationship of microorganisms.
• Generation microbiology: The study of those microorganisms that have the same characters as their parents.
• Systems microbiology: A discipline bridging systems biology and microbiology.
• Molecular microbiology: The study of the molecular principles of the physiological processes in microorganisms.

Other

• Nano microbiology: The study of those microorganisms on nano level.
• Exo microbiology (or Astro microbiology): The study of microorganisms in outer space.
• Weapon microbiology: The study of those microorganisms which are being used in weapon industries.

Applied microbiology

• Medical microbiology: The study of the pathogenic microbes and the role of microbes in human illness. Includes the study of microbial pathogenesis and epidemiology and is related to the study of disease pathology and immunology.
• Pharmaceutical microbiology: The study of microorganisms that are related to the production of antibiotics, enzymes, vitamins,vaccines, and other pharmaceutical products and that cause pharmaceutical contamination and spoil.
• Industrial microbiology: The exploitation of microbes for use in industrial processes. Examples include industrial fermentation and wastewater treatment. Closely linked to the biotechnology industry. This field also includes brewing, an important application of microbiology.
• Microbial biotechnology: The manipulation of microorganisms at the genetic and molecular level to generate useful products.
• Food microbiology and Dairy microbiology: The study of microorganisms causing food spoilage and foodborne illness. Using microorganisms to produce foods, for example by fermentation.
• Agricultural microbiology: The study of agriculturally relevant microorganisms. This field can be further classified into the following:
  • Plant microbiology and Plant pathology: The study of the interactions between microorganisms and plants and plant pathogens.
  • Soil microbiology: The study of those microorganisms that are found in soil.
• Veterinary microbiology: The study of the role in microbes in veterinary medicine or animal taxonomy.
• Environmental microbiology: The study of the function and diversity of microbes in their natural environments. This involves the characterization of key bacterial habitats such as the rhizosphere and phyllosphere, soil and groundwater ecosystems, open oceans or extreme environments (extremophiles). This field includes other branches of microbiology such as:
  • Microbial ecology
  • Microbially mediated nutrient cycling
  • Geomicrobiology
  • Microbial diversity
  • Bioremediation
• Water microbiology (or Aquatic microbiology): The study of those microorganisms that are found in water.
• Aeromicrobiology (or Air microbiology): The study of airborne microorganisms.

                           Microbiology

Microbiology  is the study of microscopic organisms, either unicellular (single cell), multicellular (cell colony), or acellular (lacking cells). Microbiology includes the disciplines virology, mycology, parasitology, bacteriology, and so on.

Eukaryotic microorganisms exhibit cell organelles and include fungi and protists, whereas prokaryotic organisms—which all are microorganisms—are conventionally classified as lacking organelles and include eubacteria and archaebacteria. Microbiologists traditionally relied on culture, staining, and microscopy. Apparently, however, only some 1% of the microorganisms present in some environments are culturable.Microbiologists often rely on extraction or detection of nucleic acid, either DNA or RNA sequences.

Viruses are not always classified as organisms, as they have been identified either as very simple microorganisms or very complex molecules. Prions, never considered microorganisms, have been investigated by virologists, however, as the clinical effects traced to them were originally presumed due to chronic viral infections, and virologists took search—discovering "infectious proteins".

Diagnosis

Chlamydia trachomatis inclusion bodies (brown) in a McCoy cell culture

                     

The diagnosis of genital chlamydial infections evolved rapidly from the 1990s through 2006. Nucleic acid amplification tests (NAAT), such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), and the DNA strand displacement amplification (SDA) now are the mainstays. NAAT for chlamydia may be performed on swab specimens collected from the cervix (women) or urethra (men), on self-collected vaginal swabs, or on voided urine. Urine and self-collected swab testing facilitates the performance of screening tests in settings where genital examination is impractical. At present, the NAATs have regulatory approval only for testing urogenital specimens, although rapidly evolving research indicates that they may give reliable results on rectal specimens.

Because of improved test accuracy, ease of specimen management, convenience in specimen management, and ease of screening sexually active men and women, the NAATs have largely replaced culture, the historic gold standard for chlamydia diagnosis, and the non-amplified probe tests. The latter test is relatively insensitive, successfully detecting only 60-80% of infections in asymptomatic women, and often giving falsely positive results. Culture remains useful in selected circumstances and is currently the only assay approved for testing non-genital specimens.

Screening

For sexually active women who are not pregnant, screening is recommended in those under 25 and others at risk of infection. Risk factors include a history of chlamydial or other sexually transmitted infection, new or multiple sexual partners, and inconsistent condom use. For pregnant women, guidelines vary: screening women with age or other risk factors is recommended by the U.S. Preventive Services Task Force (USPSTF) (which recommends screening women under 25) and the American Academy of Family Physicians (which recommends screening women aged 25 or younger). The American College of Obstetricians and Gynecologists recommends screening all at risk, while the Centers for Disease Control and Prevention recommend universal screening of pregnant women. The USPSTF acknowledges that in some communities there may be other risk factors for infection, such as ethnicity.Evidence-based recommendations for screening initiation, intervals and termination are currently not possible. There is no universal agreement on screening men for chlamydia.

In England and Wales the NHS National Chlamydia Screening Programme (NCSP) aims to

Prevent and control chlamydia infection through early detection and treatment of 
asymptomatic infection;1
Reduce onward transmission to sexual partners;2
Prevent the consequences of untreated infection;3
Test at least 25 percent of the sexually active under 25 population annually.4

Pathophysiology of Chlamydia

Pathophysiology

Chlamydiae have the ability to establish long-term associations with host cells. When an infected host cell is starved for various nutrients such as amino acids (for example, tryptophan), iron, or vitamins, this has a negative consequence for Chlamydiae since the organism is dependent on the host cell for these nutrients. Long-term cohort studies indicate that approximately 50% of those infected clear within a year, 80% within two years, and 90% within three years

The starved chlamydiae enter a persistent growth state wherein they stop cell division and become morphologically aberrant by increasing in size. Persistent organisms remain viable as they are capable of returning to a normal growth state once conditions in the host cell improve.

There is much debate as to whether persistence has in vivo relevance. Many believe that persistent chlamydiae are the cause of chronic chlamydial diseases. Some antibiotics such as β-lactams can also induce a persistent-like growth state, which can contribute to the chronicity of chlamydial diseases

Transmission of Chlamydia

Transmission

Chlamydia can be transmitted during vaginal, anal, or oral sex. Chlamydia can also be passed from an infected mother to her baby during vaginal childbirth

Chlamydia infection

                                                          Signs and symptoms

                                                                                                    Genital disease

Women

 

Chlamydial infection of the neck of the womb (cervicitis) is a sexually transmitted infection which is asymptomatic for about 50-70% of women infected with the disease. The infection can be passed through vaginal, anal, or oral sex. Of those who have an asymptomatic infection that is not detected by their doctor, approximately half will develop pelvic inflammatory disease (PID), a generic term for infection of the uterus, fallopian tubes, and/or ovaries. PID can cause scarring inside the reproductive organs, which can later cause serious complications, including chronic pelvic pain, difficulty becoming pregnant, ectopic (tubal) pregnancy, and other dangerous complications of pregnancy.

Chlamydia is known as the "Silent Epidemic" because in women, it may not cause any symptoms in 70%-80% of cases, and can linger for months or years before being discovered. Symptoms that may occur include unusual vaginal bleeding or discharge, pain in the abdomen, painful sexual intercourse (dyspareunia), fever, painful urination or the urge to urinate more frequently than usual (urinary urgency

Men

 

In men, chlamydia shows symptoms of infectious urethritis (inflammation of the urethra) in about 50% of cases. Symptoms that may occur include: a painful or burning sensation when urinating, an unusual discharge from the penis, swollen or tender testicles, or fever. Discharge, or the purulent exudate, is generally less viscous and lighter in color than for gonorrhea. If left untreated, it is possible for chlamydia in men to spread to the testicles causing epididymitis, which in rare cases can cause sterility if not treated within 6 to 8 weeks. Chlamydia is also a potential cause of prostatitis in men, although the exact relevance in prostatitis is difficult to ascertain due to possible contamination from urethritis

Eye disease

Chlamydia conjunctivitis or trachoma was once the most important cause of blindness worldwide, but its role diminished from 15% of blindness cases by trachoma in 1995 to 3.6% in 2002. The infection can be spread from eye to eye by fingers, shared towels or cloths, coughing and sneezing and eye-seeking flies. Newborns can also develop chlamydia eye infection through childbirth (see below). Using the SAFE strategy (acronym for surgery for in-growing or in-turned lashes, antibiotics, facial cleanliness, and environmental improvements), the World Health Organisation aims for the global elimination of trachoma by 2020 (GET 2020 initiative).

Rheumatological conditions

Chlamydia may also cause reactive arthritis (reiter's syndrome) - the triad of arthritis, conjunctivitis and urethritis (inflammation of the urethra) - especially in young men. About 15,000 men develop reactive arthritis due to chlamydia infection each year in the U.S., and about 5,000 are permanently affected by it. It can occur in both sexes, though is more common in men.

Perinatal infections

As many as half of all infants born to mothers with chlamydia will be born with the disease. Chlamydia can affect infants by causing spontaneous abortion; premature birth; conjunctivitis, which may lead to blindness; and pneumonia. Conjunctivitis due to chlamydia typically occurs one week after birth (compared with chemical causes (within hours) or gonorrhea (2–5 days)).

Other conditions

Chlamydia trachomatis is also the cause of lymphogranuloma venereum, an infection of the lymph nodes and lymphatics. It usually presents with genital ulceration and swollen lymph nodes in the groin, but it may also manifest as proctitis (inflammation of the rectum), fever or swollen lymph nodes in other regions of the body.

Chlamydia infection

Chlamydia
Pap smear showing C. trachomatis (H&E stain)

Chlamydia infection (from the Greek, χλαμύδα meaning "cloak") is a common sexually transmitted infection (STI) in humans caused by the bacterium Chlamydia trachomatis. The term Chlamydia infection can also refer to infection caused by any species belonging to the bacterial family Chlamydiaceae. C. trachomatis is found only in humans.. Chlamydia is a major infectious cause of human genital and eye disease. Chlamydia infection is one of the most common sexually transmitted infections worldwide; it is estimated that about 1 million individuals in the United States are infected with chlamydia.

C. trachomatis is naturally found living only inside human cells. Chlamydia can be transmitted during vaginal, anal, or oral sex, and can be passed from an infected mother to her baby during vaginal childbirth. Between half and three-quarters of all women who have a chlamydia infection of the cervix (cervicitis) have no symptoms and do not know that they are infected. In men, infection of the urethra (urethritis) is usually symptomatic, causing a white discharge from the penis with or without pain on urinating (dysuria). Occasionally, the condition spreads to the upper genital tract in women (causing pelvic inflammatory disease) or to the epididymis in men (causing epididymitis). If untreated, chlamydial infections can cause serious reproductive and other health problems with both short-term and long-term consequences.

Chlamydia conjunctivitis or trachoma is a common cause of blindness worldwide. The World Health Organization (WHO) estimates that it accounted for 15% of blindness cases in 1995, but only 3.6% in 2002.