<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Gonorrhea and explain in detail? [/INST] Gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae. Infection may involve the genitals, mouth, or rectum. Infected men may experience pain or burning with urination, discharge from the penis, or testicular pain. Infected women may experience burning with urination, vaginal discharge, vaginal bleeding between periods, or pelvic pain. Complications in women include pelvic inflammatory disease and in men include inflammation of the epididymis. Many of those infected, however, have no symptoms. If untreated, gonorrhea can spread to joints or heart valves.Gonorrhea is spread through sexual contact with an infected person. This includes oral, anal, and vaginal sex. It can also spread from a mother to a child during birth. Diagnosis is by testing the urine, urethra in males, or cervix in females. Testing all women who are sexually active and less than 25 years of age each year as well as those with new sexual partners is recommended; the same recommendation applies in men who have sex with men (MSM).Gonorrhea can be prevented with the use of condoms, having sex with only one person who is uninfected, and by not having sex. Treatment is usually with ceftriaxone by injection and azithromycin by mouth. Resistance has developed to many previously used antibiotics and higher doses of ceftriaxone are occasionally required. Retesting is recommended three months after treatment. Sexual partners from the last two months should also be treated.Gonorrhea affects about 0.8% of women and 0.6% of men. An estimated 33 to 106 million new cases occur each year, out of the 498 million new cases of curable STI – which also includes syphilis, chlamydia, and trichomoniasis. Infections in women most commonly occur when they are young adults. In 2015, it caused about 700 deaths. Descriptions of the disease date back to before the Common Era within the Old Testament. The current name was first used by the Greek physician Galen before 200 AD who referred to it as "an unwanted discharge of semen".

Signs and symptoms
Gonorrhea infections of mucosal membranes can cause swelling, itching, pain, and the formation of pus. The time from exposure to symptoms is usually between two and 14 days, with most symptoms appearing between four and six days after infection, if they appear at all.  Both men and women with infections of the throat may experience a sore throat, though such infection does not produce symptoms in 90% of cases. Other symptoms may include swollen lymph nodes around the neck. Either sex can become infected in the eyes or rectum if these tissues are exposed to the bacterium.

Women
Half of women with gonorrhea are asymptomatic but the other half experience vaginal discharge, lower abdominal pain, or pain with sexual intercourse associated with inflammation of the uterine cervix. Common medical complications of untreated gonorrhea in women include pelvic inflammatory disease which can cause scars to the fallopian tubes and result in later ectopic pregnancy among those women who become pregnant.

Men
Most infected men with symptoms have inflammation of the penile urethra associated with a burning sensation during urination and discharge from the penis. In men, discharge with or without burning occurs in half of all cases and is the most common symptom of the infection. This pain is caused by a narrowing and stiffening of the urethral lumen. The most common medical complication of gonorrhea in men is inflammation of the epididymis. Gonorrhea is also associated with increased risk of prostate cancer.

Infants
If not treated, gonococcal ophthalmia neonatorum will develop in 28% of infants born to women with gonorrhea.

Spread
If left untreated, gonorrhea can spread from the original site of infection and infect and damage the joints, skin, and other organs. Indications of this can include fever, skin rashes, sores, and joint pain and swelling. In advanced cases, gonorrhea may cause a general feeling of tiredness similar to other infections. It is also possible for an individual to have an allergic reaction to the bacteria, in which case any appearing symptoms will be greatly intensified. Very rarely it may settle in the heart, causing endocarditis, or in the spinal column, causing meningitis. Both are more likely among individuals with suppressed immune systems, however.

Cause
Gonorrhea is caused by the bacterium Neisseria gonorrhoeae. Previous infection does not confer immunity – a person who has been infected can become infected again by exposure to someone who is infected. Infected persons may be able to infect others repeatedly without having any signs or symptoms of their own.

Spread
The infection is usually spread from one person to another through vaginal, oral, or anal sex. Men have a 20% risk of getting the infection from a single act of vaginal intercourse with an infected woman. The risk for men who have sex with men (MSM) is higher. Insertive MSM may get a penile infection from anal intercourse, while receptive MSM may get anorectal gonorrhea. Women have a 60–80% risk of getting the infection from a single act of vaginal intercourse with an infected man.A mother may transmit gonorrhea to her newborn during childbirth; when affecting the infants eyes, it is referred to as ophthalmia neonatorum. It may be able to spread through the objects contaminated with body fluid from an infected person. The bacteria typically does not survive long outside the body, typically dying within minutes to hours.

Risk factors
It is discovered that sexually active women younger than 25 and men who have sex with men are at increased risk of getting gonorrhea.Other risk factors include:

Having a new sex partner
Having a sex partner who has other partners
Having more than one sex partner
Having had gonorrhea or another sexually transmitted infection

Complications
Medically it has been said that Untreated gonorrhea can lead to major complications, such as:

Infertility in women. Gonorrhea can spread into the uterus and fallopian tubes, causing pelvic inflammatory disease (PID). PID can result in scarring of the tubes, greater risk of pregnancy complications and infertility. PID requires immediate treatment.
Infertility in men. Gonorrhea can cause a small, coiled tube in the rear portion of the testicles where the sperm ducts are located (epididymis) to become inflamed (epididymitis). Untreated epididymitis can lead to infertility.
Infection that spreads to the joints and other areas of the body. The bacterium that causes gonorrhea can spread through the bloodstream and infect other parts of the body, including the joints. Fever, rash, skin sores, joint pain, swelling and stiffness are possible results.
Increased risk of HIV/AIDS. Having gonorrhea increases the susceptibility to infection with human immunodeficiency virus (HIV), the virus that leads to AIDS. People who have both gonorrhea and HIV (untreated by anti-retroviral therapy) are able to pass both diseases more readily to their partners.
Complications in babies. Babies who contract gonorrhea from their mothers during birth can develop blindness, sores on the scalp and infections.

Diagnosis
Traditionally, gonorrhea was diagnosed with Gram stain and culture; however, newer polymerase chain reaction (PCR)-based testing methods are becoming more common. In those failing initial treatment, culture should be done to determine sensitivity to antibiotics.Tests that use PCR (aka nucleic acid amplification) to identify genes unique to N. gonorrhoeae are recommended for screening and diagnosis of gonorrhea infection. These PCR-based tests require a sample of urine, urethral swabs, or cervical/vaginal swabs. Culture (growing colonies of bacteria in order to isolate and identify them) and Gram-stain (staining of bacterial cell walls to reveal morphology) can also be used to detect the presence of N. gonorrhoeae in all specimen types except urine.If Gram-negative, oxidase-positive diplococci are visualized on direct Gram stain of urethral pus (male genital infection), no further testing is needed to establish the diagnosis of gonorrhea infection. However, in the case of female infection direct Gram stain of cervical swabs is not useful because the N. gonorrhoeae organisms are less concentrated in these samples. The chances of false positives are increased as Gram-negative diplococci native to the normal vaginal flora cannot be distinguished from N. gonorrhoeae. Thus, cervical swabs must be cultured under the conditions described above. If oxidase positive, Gram-negative diplococci are isolated from a culture of a cervical/vaginal swab specimen, then the diagnosis is made. Culture is especially useful for diagnosis of infections of the throat, rectum, eyes, blood, or joints—areas where PCR-based tests are not well established in all labs. Culture is also useful for antimicrobial sensitivity testing, treatment failure, and epidemiological purposes (outbreaks, surveillance).In patients who may have disseminated gonococcal infection (DGI), all possible mucosal sites should be cultured (e.g., pharynx, cervix, urethra, rectum). Three sets of blood cultures should also be obtained. Synovial fluid should be collected in cases of septic arthritis.All people testing positive for gonorrhea should be tested for other sexually transmitted diseases such as chlamydia, syphilis, and human immunodeficiency virus. Studies have found co-infection with chlamydia ranging from 46 to 54% in young people with gonorrhea. Among persons in the United States between 14 and 39 years of age, 46% of people with gonorrheal infection also have chlamydial infection. For this reason, gonorrhea and chlamydia testing are often combined. People diagnosed with gonorrhea infection have a fivefold increase risk of HIV transmission. Additionally, infected persons who are HIV positive are more likely to shed and transmit HIV to uninfected partners during an episode of gonorrhea.

Screening
The United States Preventive Services Task Force (USPSTF) recommends screening for gonorrhea in women at increased risk of infection, which includes all sexually active women younger than 25 years. Extragenital gonorrhea and chlamydia are highest in men who have sex with men (MSM). Additionally, the USPSTF also recommends routine screening in people who have previously tested positive for gonorrhea or have multiple sexual partners and individuals who use condoms inconsistently, provide sexual favors for money, or have sex while under the influence of alcohol or drugs.Screening for gonorrhea in women who are (or intend to become) pregnant, and who are found to be at high risk for sexually transmitted diseases, is recommended as part of prenatal care in the United States.

Prevention
As with most sexually transmitted diseases, the risk of infection can be reduced significantly by the correct use of condoms, not having sex, or can be removed almost entirely by limiting sexual activities to a mutually monogamous relationship with an uninfected person.Those previously infected are encouraged to return for follow up care to make sure that the infection has been eliminated. In addition to the use of phone contact, the use of email and text messaging have been found to improve the re-testing for infection.Newborn babies coming through the birth canal are given erythromycin ointment in the eyes to prevent blindness from infection. The underlying gonorrhea should be treated; if this is done then usually a good prognosis will follow.

Treatment
Antibiotics
Antibiotics are used to treat gonorrhea infections. As of 2016, both ceftriaxone by injection and azithromycin by mouth are most effective. However, due to increasing rates of antibiotic resistance, local susceptibility patterns must be taken into account when deciding on treatment. Ertapenem is a potential effective alternative treatment for ceftriaxone-resistant gonorrhea.Adults may have eyes infected with gonorrhoea and require proper personal hygiene and medications. Addition of topical antibiotics have not been shown to improve cure rates compared to oral antibiotics alone in treatment of eye infected gonorrhea. For newborns, erythromycin ointment is recommended as a preventative measure for gonococcal infant conjunctivitis.Infections of the throat can be especially problematic, as antibiotics have difficulty becoming sufficiently concentrated there to destroy the bacteria. This is amplified by the fact that pharyngeal gonorrhoea is mostly asymptomatic, and gonococci and commensal Neisseria species can coexist for long time periods in the pharynx and share anti-microbial resistance genes. Accordingly, an enhanced focus on early detection (i.e., screening of high-risk populations, such as men who have sex with men, PCR testing should be considered) and appropriate treatment of pharyngeal gonorrhoea is important.

Sexual partners
It is recommended that sexual partners be tested and potentially treated. One option for treating sexual partners of people infected is patient-delivered partner therapy (PDPT), which involves providing prescriptions or medications to the person to take to his/her partner without the health care providers first examining him/her.The United States Centers for Disease Control and Prevention (CDC) currently recommend that individuals who have been diagnosed and treated for gonorrhea avoid sexual contact with others until at least one week past the final day of treatment in order to prevent the spread of the bacterium.

Antibiotic resistance
Many antibiotics that were once effective including penicillin, tetracycline, and fluoroquinolones are no longer recommended because of high rates of resistance. Resistance to cefixime has reached a level such that it is no longer recommended as a first-line agent in the United States, and if it is used a person should be tested again after a week to determine whether the infection still persists. Public health officials are concerned that an emerging pattern of resistance may predict a global epidemic. In 2016, the WHO published new guidelines for treatment, stating "There is an urgent need to update treatment recommendations for gonococcal infections to respond to changing antimicrobial resistance (AMR) patterns of N. gonorrhoeae. High-level resistance to previously recommended quinolones is widespread and decreased susceptibility to the extended-spectrum (third-generation) cephalosporins, another recommended first-line treatment in the 2003 guidelines, is increasing and several countries have reported treatment failures."

Prognosis
Gonorrhea if left untreated may last for weeks or months with higher risks of complications. One of the complications of gonorrhea is systemic dissemination resulting in skin pustules or petechia, septic arthritis, meningitis, or endocarditis. This occurs in between 0.6 and 3% of infected women and 0.4 and 0.7% of infected men.In men, inflammation of the epididymis, prostate gland, and urethra can result from untreated gonorrhea. In women, the most common result of untreated gonorrhea is pelvic inflammatory disease. Other complications include inflammation of the tissue surrounding the liver, a rare complication associated with Fitz-Hugh–Curtis syndrome; septic arthritis in the fingers, wrists, toes, and ankles; septic abortion; chorioamnionitis during pregnancy; neonatal or adult blindness from conjunctivitis; and infertility. Men who have had a gonorrhea infection have an increased risk of getting prostate cancer.

Epidemiology
About 88 million cases of gonorrhea occur each year, out of the 448 million new cases of curable STI each year – that also includes syphilis, chlamydia and trichomoniasis. The prevalence was highest in the African region, the Americas, and Western Pacific, and lowest in Europe. In 2013, it caused about 3,200 deaths, up from 2,300 in 1990.In the United Kingdom, 196 per 100,000 males 20 to 24 years old and 133 per 100,000 females 16 to 19 years old were diagnosed in 2005. In 2013, the CDC estimated that more than 820,000 people in the United States get a new gonorrheal infection each year. Fewer than half of these infections are reported to CDC. In 2011, 321,849 cases of gonorrhea were reported to the CDC. After the implementation of a national gonorrhea control program in the mid-1970s, the national gonorrhea rate declined from 1975 to 1997. After a small increase in 1998, the gonorrhea rate has decreased slightly since 1999. In 2004, the rate of reported gonorrheal infections was 113. 5 per 100,000 persons.In the US, it is the second-most-common bacterial sexually transmitted infections; chlamydia remains first. According to the CDC African Americans are most affected by gonorrhea, accounting for 69% of all gonorrhea cases in 2010.The World Health Organization warned in 2017 of the spread of untreatable strains of gonorrhea, following analysis of at least three cases in Japan, France and Spain, which survived all antibiotic treatment.

History
Some scholars translate the biblical terms zav (for a male) and zavah (for a female) as gonorrhea.It has been suggested that mercury was used as a treatment for gonorrhea. Surgeons tools on board the recovered English warship the Mary Rose included a syringe that, according to some, was used to inject the mercury via the urinary meatus into crewmen with gonorrhea. The name "the clap", in reference to the disease, is recorded as early as the sixteenth century, referring to a medieval red-light district in Paris, Les Clapiers. Translating to "The rabbit holes", it was so named for the small huts in which prostitutes worked.In 1854, Dr. Wilhelm Gollmann addressed gonorrhea in his book, Homeopathic Guide to all Diseases Urinary and Sexual Organs. He noted that the disease was common in prostitutes and homosexuals in large cities. Gollmann recommended the following as cures: aconite to cure "shooting pains with soreness and inflammation;" mercury "for stitching pain with purulent discharge;" nux vomica and sulphur "when the symptoms are complicated with hemorrhoids and stricture of the rectum. Other remedies include argentum, aurum (gold), belladonna, calcarea, ignatia, phosphorus, and sepia.Silver nitrate was one of the widely used drugs in the 19th century. However, it became replaced by Protargol. Arthur Eichengrün invented this type of colloidal silver, which was marketed by Bayer from 1897 onward. The silver-based treatment was used until the first antibiotics came into use in the 1940s.The exact time of onset of gonorrhea as prevalent disease or epidemic cannot be accurately determined from the historical record. One of the first reliable notations occurs in the Acts of the (English) Parliament. In 1161, this body passed a law to reduce the spread of "... the perilous infirmity of burning". The symptoms described are consistent with, but not diagnostic of, gonorrhea. A similar decree was passed by Louis IX in France in 1256, replacing regulation with banishment. Similar symptoms were noted at the siege of Acre by Crusaders.
Coincidental to, or dependent on, the appearance of a gonorrhea epidemic, several changes occurred in European medieval society </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Wolff–Parkinson–White syndrome and explain in detail? [/INST] Wolff–Parkinson–White syndrome (WPWS) is a disorder due to a specific type of problem with the electrical system of the heart. About 60% of people with the electrical problem developed symptoms, which may include an abnormally fast heartbeat, palpitations, shortness of breath, lightheadedness, or syncope. Rarely, cardiac arrest may occur. The most common type of irregular heartbeat that occurs is known as paroxysmal supraventricular tachycardia.The cause of WPW is typically unknown and is likely due to a combination of chance and genetic factors. A small number of cases are due to a mutation of the PRKAG2 gene which may be inherited from a persons parents in an autosomal dominant fashion. The underlying mechanism involves an accessory electrical conduction pathway between the atria and the ventricles. It is associated with other conditions such as Ebstein anomaly and hypokalemic periodic paralysis. The diagnosis of WPW occurs with a combination of palpitations and when an electrocardiogram (ECG) show a short PR interval and a delta wave. It is a type of pre-excitation syndrome.WPW syndrome may be monitored or treated with either medications or an ablation (destroying the tissues) such as with radiofrequency catheter ablation. It affects between 0.1 and 0.3% in the population. The risk of death in those without symptoms is about 0.5% per year in children and 0.1% per year in adults. In some cases, non-invasive monitoring may help to more carefully risk stratify patients into a lower risk category.  In those without symptoms ongoing observation may be reasonable.  In those with WPW complicated by atrial fibrillation, cardioversion or the medication procainamide may be used. The condition is named after Louis Wolff, John Parkinson, and Paul Dudley White who described the ECG findings in 1930.

Signs and symptoms
People with WPW are usually asymptomatic when not having a fast heart rate.  However, individuals may experience palpitations, dizziness, shortness of breath, or infrequently syncope (fainting or near fainting) during episodes of supraventricular tachycardia.  WPW is also associated with a very small risk of sudden death due to more dangerous heart rhythm disturbances.

Pathophysiology
Electrical activity in the normal human heart begins when a cardiac action potential arises in the sinoatrial (SA) node, which is located in the right atrium. From there, the electrical stimulus is transmitted via internodal pathways to the atrioventricular (AV) node. After a brief delay at the AV node, the stimulus travels through the bundle of His to the left and right bundle branches and then to the Purkinje fibers and the endocardium at the apex of the heart, then finally to the ventricular myocardium.The AV node serves an important function as a "gatekeeper", limiting the electrical activity that reaches the ventricles. In situations where the atria generate excessively rapid electrical activity (such as atrial fibrillation or atrial flutter), the AV node limits the number of signals conducted to the ventricles. For example, if the atria are electrically activated at 300 beats per minute, half those electrical impulses may be blocked by the AV node, so that the ventricles are stimulated at only 150 beats per minute – resulting in a pulse of 150 beats per minute. Another important property of the AV node is that it slows down individual electrical impulses. This is manifested on the electrocardiogram as the PR interval (the time from electrical activation of the atria to electrical activation of the ventricles), which is usually shortened to less than 120 milliseconds in duration.Individuals with WPW have an accessory pathway that communicates between the atria and the ventricles, in addition to the AV node. This accessory pathway is known as the bundle of Kent. This accessory pathway does not share the rate-slowing properties of the AV node and may conduct electrical activity at a significantly higher rate than the AV node. For instance, in the example above, if an individual had an atrial rate of 300 beats per minute, the accessory bundle may conduct all the electrical impulses from the atria to the ventricles, causing the ventricles to contract at 300 beats per minute. Extremely rapid heart rates such as this may result in hemodynamic instability or cardiogenic shock. In some cases, the combination of an accessory pathway and abnormal heart rhythms can trigger ventricular fibrillation, a leading cause of sudden cardiac death.WPW may be associated with PRKAG2, a protein kinase enzyme encoded by the PRKAG2 gene.

Bundle of Kent
The bundle of Kent is an abnormal extra or accessory conduction pathway between the atria and ventricles that is present in a small percentage (between 0.1 and 0.3%) of the general population. This pathway may communicate between the left atrium and the left ventricle, in which case it is termed a "type A pre-excitation", or between the right atrium and the right ventricle, in which case it is termed a "type B pre-excitation" in old, currently abandoned classification. Problems arise when this pathway creates an electrical circuit that bypasses the AV node. The AV node is capable of slowing the rate of conduction of electrical impulses to the ventricles, whereas the bundle of Kent lacks this capability. When an aberrant electrical connection is made via the bundle of Kent, tachydysrhythmias may therefore result.

Diagnosis
WPW is commonly diagnosed on the basis of the electrocardiogram in an asymptomatic individual. In this case, it is manifested as a delta wave, which is a slurred upstroke in the QRS complex that is associated with a short PR interval. The short PR interval and slurring of the QRS complex are reflective of the impulse making it to the ventricles early (via the accessory pathway) without the usual delay experienced in the AV node.If a person with WPW experiences episodes of atrial fibrillation, the ECG shows a rapid polymorphic wide-complex tachycardia (without torsades de pointes). This combination of atrial fibrillation and WPW is considered dangerous, and most antiarrhythmic drugs are contraindicated.When an individual is in normal sinus rhythm, the ECG characteristics of WPW are a short PR interval (less than 120 milliseconds in duration), widened QRS complex (greater than 120 milliseconds in duration) with slurred upstroke of the QRS complex, and secondary repolarization changes (reflected in ST segment-T wave changes).In individuals with WPW, electrical activity that is initiated in the SA node travels through the accessory pathway, as well as through the AV node to activate the ventricles via both pathways. Since the accessory pathway does not have the impulse slowing properties of the AV node, the electrical impulse first activates the ventricles via the accessory pathway, and immediately afterwards via the AV node. This gives the short PR interval and slurred upstroke of the QRS complex known as the delta wave.In case of type A pre-excitation (left atrioventricular connections), a positive R wave is seen in V1 ("positive delta") on the precordial leads of the electrocardiogram, while in type B pre-excitation (right atrioventricular connections), a predominantly negative delta wave is seen in lead V1 ("negative delta").People with WPW may have more than one accessory pathway – in some cases, as many as eight abnormal pathways have been found. This has been seen in individuals with Ebsteins anomaly.Wolff–Parkinson–White syndrome is sometimes associated with Lebers hereditary optic neuropathy, a form of mitochondrial disease.

Risk stratification
WPW carries a small risk of sudden death, presumably due to rapidly conducted atrial fibrillation causing ventricular fibrillation.  While the overall risk is approximately 2.4 per 1000 person years, the risk in an individual is dependent on the properties of the accessory pathway causing pre-excitation.A higher risk accessory pathway may be suggested by a history of syncope, but risk stratification is best performed by assessing how frequently a pathway can conduct impulse to the ventricles, usually via programmed electrical stimulation (PES) in the cardiac electrophysiology laboratory. This is an invasive but generally low-risk procedure during which the atria are stimulated to try to induce tachycardia. If a tachycardia involving the accessory pathway can be triggered, the cardiologist can then assess how rapidly the accessory pathway is able to conduct. The faster it can conduct, the higher the likelihood the accessory pathway can conduct fast enough to trigger a lethal tachycardia.High-risk features that may be present during PES include an effective refractory period of the accessory pathway less than 250 ms, multiple pathways, septal location of pathway, and inducibility of supraventricular tachycardia (AVRT, atrial fibrillation). Individuals with any of these high-risk features are generally considered at increased risk for SCD or symptomatic tachycardia, and should be treated accordingly (i.e.: catheter ablation).It is unclear whether invasive risk stratification (with PES) is necessary in the asymptomatic individual. While some groups advocate PES for risk stratification in all individuals under 35 years old, others only offer it to individuals who have history suggestive of a tachydysrhythmia, since the incidence of sudden cardiac death is so low (less than 0.6% in some reports).Other methods of risk stratification include observing the ventricular rate during spontaneous atrial fibrillation on a 12-lead ECG.  RR intervals of less than 250 ms suggest a higher risk pathway.  During exercise testing, abrupt loss of pre-excitation as heart rate increases also suggest a lower risk pathway. However, this approach is hampered by the normal improvement in AV node conduction during exercise which can also mask pre-excitation despite ongoing conduction down the accessory pathway.

Treatment
According to the ACLS protocol, people with WPW who are experiencing rapid abnormal heart rhythms (tachydysrhythmias) may require synchronized electrical cardioversion if they are demonstrating severe signs or symptoms (for example, low blood pressure or lethargy with altered mental status). If they are relatively stable, medication may be used.

Medications
WPW pattern with hemodynamically stability and orthodromic AVRT leading to a regular narrow complex tachycardia may be managed similarly to other regular narrow complex supraventricular tachycardias: first with vagal maneuvers followed by a trial of adenosine (first-line therapy). The 2015 ACC/AHA/HRS guidelines recommend beta-blockers or calcium channel blockers as second-line agents, electric cardioversion is reserved for refractory arrhythmias. However, if there is any doubt about the diagnosis of orthodromic AVRT or if aberrant conduction leading to a wide complex QRS is observed, it may be prudent to manage as undifferentiated wide complex tachycardia. People with atrial fibrillation and rapid ventricular response may be treated with amiodarone or procainamide to stabilize their heart rate. Procainamide and cardioversion are accepted treatments for conversion of tachycardia found with WPW. Amiodarone in atrial fibrillation with WPW, is linked to ventricular fibrillation, and thus may be worse than procainamide.AV node blockers should be avoided in atrial fibrillation and atrial flutter with WPW or history of it; this includes adenosine, diltiazem, verapamil, other calcium channel blockers, and beta blockers </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Ventricular septal defect and explain in detail? [/INST] A ventricular septal defect (VSD) is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart. The extent of the opening may vary from pin size to complete absence of the ventricular septum, creating one common ventricle. The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.
The membranous portion, which is close to the atrioventricular node, is most commonly affected in adults and older children in the United States. It is also the type that will most commonly require surgical intervention, comprising over 80% of cases.Membranous ventricular septal defects are more common than muscular ventricular septal defects, and are the most common congenital cardiac anomaly.

Signs and symptoms
Ventricular septal defect is usually symptomless at birth. It usually manifests a few weeks after birth.VSD is an acyanotic congenital heart defect, aka a left-to-right shunt, so there are no signs of cyanosis in the early stage. However, uncorrected VSD can increase pulmonary resistance leading to the reversal of the shunt and corresponding cyanosis.
Pansystolic (Holosystolic) murmur along lower left sternal border (depending upon the size of the defect) +/- palpable thrill (palpable turbulence of blood flow). Heart sounds are normal. Larger VSDs may cause a parasternal heave, a displaced apex beat (the palpable heartbeat moves laterally over time, as the heart enlarges). An infant with a large VSD will fail to thrive and become sweaty and tachypnoeic (breathe faster) with feeds.The restrictive ventricular septal defects (smaller defects) are associated with a louder murmur and more palpable thrill (grade IV murmur). Larger defects may eventually be associated with pulmonary hypertension due to the increased blood flow. Over time this may lead to an Eisenmengers syndrome the original VSD operating with a left-to-right shunt, now becomes a right-to-left shunt because of the increased pressures in the pulmonary vascular bed.

Cause
Congenital VSDs are frequently associated with other congenital conditions, such as Down syndrome.A VSD can also form a few days after a myocardial infarction (heart attack) due to mechanical tearing of the septal wall, before scar tissue forms, when macrophages start remodeling the dead heart tissue.
A congenital VSD can result from a disturbance in the morphogenesis of the heart in its embryonic stages. In the fifth week of gestation, the heart undergoes multiple processes of septation and forming a dextral loop. Interfering with the latter leads to insufficient leftward movement of the ventricular outflow tract over the atrioventricular canal, which in turn can result in a VSD or, in the most extreme cases, a double outlet right ventricle with one.A ventricular septal defect arises when the superior part of the interventricular septum, which separates the right and left ventricles of the heart, fails to fully develop. The right ventricle pumps blood to the lungs to get oxygen, while the left ventricle pumps blood to the rest of the body to provide oxygen to tissues. A ventricular septal defect results in the mixing of oxygen-rich blood with oxygen-poor blood, increasing strain on the heart and lungs.

Pathophysiology
During ventricular contraction, or systole, some of the blood from the left ventricle leaks into the right ventricle, passes through the lungs and reenters the left ventricle via the pulmonary veins and left atrium.  This has two net effects.  First, the circuitous refluxing of blood causes volume overload on the left ventricle.  Second, because the left ventricle normally has a much higher systolic pressure (~120 mmHg) than the right ventricle (~20 mmHg), the leakage of blood into the right ventricle therefore elevates right ventricular pressure and volume, causing pulmonary hypertension with its associated symptoms.
In serious cases, the pulmonary arterial pressure can reach levels that equal the systemic pressure. This reverses the left to right shunt, so that blood then flows from the right ventricle into the left ventricle, resulting in cyanosis, as blood is by-passing the lungs for oxygenation.This effect is more noticeable in patients with larger defects, who may present with breathlessness, poor feeding and failure to thrive in infancy. Patients with smaller defects may be asymptomatic. Four different septal defects exist, with perimembranous most common, outlet, atrioventricular, and muscular less commonly.

Diagnosis
A VSD can be detected by cardiac auscultation.  Classically, a VSD causes a pathognomonic holo- or pansystolic murmur.  Auscultation is generally considered sufficient for detecting a significant VSD. The murmur depends on the abnormal flow of blood from the left ventricle, through the VSD, to the right ventricle.  If there is not much difference in pressure between the left and right ventricles, then the flow of blood through the VSD will not be very great and the VSD may be silent.  This situation occurs a) in the fetus (when the right and left ventricular pressures are essentially equal), b) for a short time after birth (before the right ventricular pressure has decreased), and c) as a late complication of unrepaired VSD.  Confirmation of cardiac auscultation can be obtained by non-invasive cardiac ultrasound (echocardiography).  To more accurately measure ventricular pressures, cardiac catheterization, can be performed.

Classification
Although there are several classifications for VSD, the most accepted and unified classification is that of Congenital Heart Surgery Nomenclature and Database Project.
The classification is based on the location of the VSD on the right ventricular surface of the inter ventricular septum and is as follows:

Multiple
Type 1
Type 1 is sub aortic

Type 2
Type 2 also known as perimembranous, paramembranous, conoventricular, membranous septal defect, and subaortic.
Most common variety found in 70%

Type 3
Type 3 also known as inlet (or AV canal type).

Commonly associated with atrioventricular septal defect, found in about 5%

Type 4
Type 4 also known as muscular (trabecular)

Located in the muscular septum, found in 20%. Can be sub classified again based on the location into anterior, apical, posterior and mid

Type: Gerbode
Type: Gerbode also known as left ventricular to right atrial communication

Due to absence of Atrioventricular septum.

Treatment
Most cases do not need treatment and heal during the first years of life. Treatment is either conservative or surgical.  Smaller congenital VSDs often close on their own, as the heart grows, and in such cases may be treated conservatively.
Some cases may necessitate surgical intervention, i.e. with the following indications:

Failure of congestive cardiac failure to respond to medications
VSD with pulmonic stenosis
Large VSD with pulmonary hypertension
VSD with aortic regurgitationFor the surgical procedure, a heart-lung machine is required and a median sternotomy is performed.  Percutaneous endovascular procedures are less invasive and can be done on a beating heart, but are only suitable for certain patients.  Repair of most VSDs is complicated by the fact that the conducting system of the heart is in the immediate vicinity.
Ventricular septum defect in infants is initially treated medically with cardiac glycosides (e.g., digoxin 10-20 μg/kg per day), loop diuretics (e.g., furosemide 1–3 mg/kg per day) and ACE inhibitors (e.g., captopril 0.5–2 mg/kg per day).

Transcatheter closure
A device, known as the Amplatzer muscular VSD occluder, may be used to close certain VSDs. It was initially approved in 2009. It appears to work well and be safe. The cost is also lower than having open heart surgery. The device is placed through a small incision in the groin.The Amplatzer septal occluder was shown to have full closure of the ventricular defect within the 24 hours of placement.  It has a low risk of embolism after implantation.  Some tricuspid valve regurgitation was shown after the procedure that could possibly be due from the right ventricular disc.  There have been some reports that the Amplatzer septal occluder may cause life-threatening erosion of the tissue inside the heart. This occurs in one percent of people implanted with the device and requires immediate open-heart surgery.  This erosion occurs due to improper sizing of the device resulting with it being too large for the defect, causing rubbing of the septal tissue and erosion.

Surgery
Surgical closure of a Perimembranous VSD is performed on cardiopulmonary bypass with ischemic arrest </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Yellow fever and explain in detail? [/INST] Yellow fever is a viral disease of typically short duration. In most cases, symptoms include fever, chills, loss of appetite, nausea, muscle pains – particularly in the back – and headaches. Symptoms typically improve within five days. In about 15% of people, within a day of improving the fever comes back, abdominal pain occurs, and liver damage begins causing yellow skin. If this occurs, the risk of bleeding and kidney problems is increased.The disease is caused by the yellow fever virus and is spread by the bite of an infected mosquito. It infects only humans, other primates, and several types of mosquitoes. In cities, it is spread primarily by Aedes aegypti, a type of mosquito found throughout the tropics and subtropics. The virus is an RNA virus of the genus Flavivirus. The disease may be difficult to tell apart from other illnesses, especially in the early stages. To confirm a suspected case, blood-sample testing with polymerase chain reaction is required.A safe and effective vaccine against yellow fever exists, and some countries require vaccinations for travelers. Other efforts to prevent infection include reducing the population of the transmitting mosquitoes. In areas where yellow fever is common, early diagnosis of cases and immunization of large parts of the population are important to prevent outbreaks. Once a person is infected, management is symptomatic; no specific measures are effective against the virus. Death occurs in up to half of those who get severe disease.In 2013, yellow fever resulted in about 127,050 severe infections and 45,000 deaths worldwide, with nearly 90 percent of these occurring in Africa. Nearly a billion people live in an area of the world where the disease is common. It is common in tropical areas of the continents of South America and Africa, but not in Asia. Since the 1980s, the number of cases of yellow fever has been increasing. This is believed to be due to fewer people being immune, more people living in cities, people moving frequently, and changing climate increasing the habitat for mosquitoes.The disease originated in Africa and spread to the Americas starting in the 15th century with the European trafficking of enslaved Africans from sub-Saharan Africa. Since the 17th century, several major outbreaks of the disease have occurred in the Americas, Africa, and Europe. In the 18th and 19th centuries, yellow fever was considered one of the most dangerous infectious diseases; numerous epidemics swept through major cities of the US and in other parts of the world.In 1927, yellow fever virus was the first human virus to be isolated.

Signs and symptoms
Yellow fever begins after an incubation period of three to six days. Most cases cause only a mild infection with fever, headache, chills, back pain, fatigue, loss of appetite, muscle pain, nausea, and vomiting. In these cases, the infection lasts only three to six days.But in 15% of cases, people enter a second, toxic phase of the disease characterized by recurring fever, this time accompanied by jaundice due to liver damage, as well as abdominal pain. Bleeding in the mouth, nose, the eyes, and the gastrointestinal tract cause vomit containing blood, hence the Spanish name for yellow fever, vómito negro ("black vomit"). There may also be kidney failure, hiccups, and delirium.Among those who develop jaundice, the fatality rate is 20 to 50%, while the overall fatality rate is about 3 to 7.5%. Severe cases may have a mortality greater than 50%.Surviving the infection provides lifelong immunity, and normally results in no permanent organ damage.

Complication
Yellow fever can lead to death for 20% to 50% of those who develop severe disease. Jaundice, fatigue, heart rhythm problems, seizures and internal bleeding may also appear as complications of yellow fever during recovery time.

Cause
Yellow fever is caused by yellow fever virus, an enveloped RNA virus 40–50 nm in width, the type species and namesake of the family Flaviviridae. It was the first illness shown to be transmissible by filtered human serum and transmitted by mosquitoes, by American doctor Walter Reed around 1900. The positive-sense, single-stranded RNA is around 10,862 nucleotides long and has a single open reading frame encoding a polyprotein.Host proteases cut this polyprotein into three structural (C, prM, E) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5); the enumeration corresponds to the arrangement of the protein coding genes in the genome. Minimal yellow fever virus (YFV) 3UTR region is required for stalling of the host 5-3 exonuclease XRN1. The UTR contains PKS3 pseudoknot structure, which serves as a molecular signal to stall the exonuclease and is the only viral requirement for subgenomic flavivirus RNA (sfRNA) production. The sfRNAs are a result of incomplete degradation of the viral genome by the exonuclease and are important for viral pathogenicity. Yellow fever belongs to the group of hemorrhagic fevers.The viruses infect, amongst others, monocytes, macrophages, Schwann cells, and dendritic cells. They attach to the cell surfaces via specific receptors and are taken up by an endosomal vesicle. Inside the endosome, the decreased pH induces the fusion of the endosomal membrane with the virus envelope. The capsid enters the cytosol, decays, and releases the genome. Receptor binding, as well as membrane fusion, are catalyzed by the protein E, which changes its conformation at low pH, causing a rearrangement of the 90 homodimers to 60 homotrimers.After entering the host cell, the viral genome is replicated in the rough endoplasmic reticulum (ER) and in the so-called vesicle packets. At first, an immature form of the virus particle is produced inside the ER, whose M-protein is not yet cleaved to its mature form, so is denoted as precursor M (prM) and forms a complex with protein E. The immature particles are processed in the Golgi apparatus by the host protein furin, which cleaves prM to M. This releases E from the complex, which can now take its place in the mature, infectious virion.

Transmission
Yellow fever virus is mainly transmitted through the bite of the yellow fever mosquito Aedes aegypti, but other mostly Aedes mosquitoes such as the tiger mosquito (Aedes albopictus) can also serve as a vector for this virus. Like other arboviruses, which are transmitted by mosquitoes, yellow fever virus is taken up by a female mosquito when it ingests the blood of an infected human or another primate. Viruses reach the stomach of the mosquito, and if the virus concentration is high enough, the virions can infect epithelial cells and replicate there. From there, they reach the haemocoel (the blood system of mosquitoes) and from there the salivary glands. When the mosquito next sucks blood, it injects its saliva into the wound, and the virus reaches the bloodstream of the bitten person. Transovarial transmissionial and transstadial transmission of yellow fever virus within A. aegypti, that is, the transmission from a female mosquito to its eggs and then larvae, are indicated. This infection of vectors without a previous blood meal seems to play a role in single, sudden breakouts of the disease.Three epidemiologically different infectious cycles occur in which the virus is transmitted from mosquitoes to humans or other primates. In the "urban cycle", only the yellow fever mosquito A. aegypti is involved. It is well adapted to urban areas, and can also transmit other diseases, including Zika fever, dengue fever, and chikungunya. The urban cycle is responsible for the major outbreaks of yellow fever that occur in Africa. Except for an outbreak in Bolivia in 1999, this urban cycle no longer exists in South America.Besides the urban cycle, both in Africa and South America, a sylvatic cycle (forest or jungle cycle) is present, where Aedes africanus (in Africa) or mosquitoes of the genus Haemagogus and Sabethes (in South America) serve as vectors. In the jungle, the mosquitoes infect mainly nonhuman primates; the disease is mostly asymptomatic in African primates. In South America, the sylvatic cycle is currently the only way humans can become infected, which explains the low incidence of yellow fever cases on the continent. People who become infected in the jungle can carry the virus to urban areas, where A. aegypti acts as a vector. Because of this sylvatic cycle, yellow fever cannot be eradicated except by eradicating the mosquitoes that serve as vectors.In Africa, a third infectious cycle known as "savannah cycle" or intermediate cycle, occurs between the jungle and urban cycles. Different mosquitoes of the genus Aedes are involved. In recent years, this has been the most common form of transmission of yellow fever in Africa.Concern exists about yellow fever spreading to southeast Asia, where its vector A. aegypti already occurs.

Pathogenesis
After transmission from a mosquito, the viruses replicate in the lymph nodes and infect dendritic cells in particular. From there, they reach the liver and infect hepatocytes (probably indirectly via Kupffer cells), which leads to eosinophilic degradation of these cells and to the release of cytokines. Apoptotic masses known as Councilman bodies appear in the cytoplasm of hepatocytes.Fatality may occur when cytokine storm, shock, and multiple organ failure follow.

Diagnosis
Yellow fever is most frequently a clinical diagnosis, based on symptomatology and travel history. Mild cases of the disease can only be confirmed virologically. Since mild cases of yellow fever can also contribute significantly to regional outbreaks, every suspected case of yellow fever (involving symptoms of fever, pain, nausea, and vomiting 6–10 days after leaving the affected area) is treated seriously.If yellow fever is suspected, the virus cannot be confirmed until 6–10 days following the illness. A direct confirmation can be obtained by reverse transcription polymerase chain reaction, where the genome of the virus is amplified. Another direct approach is the isolation of the virus and its growth in cell culture using blood plasma; this can take 1–4 weeks.Serologically, an enzyme-linked immunosorbent assay during the acute phase of the disease using specific IgM against yellow fever or an increase in specific IgG titer (compared to an earlier sample) can confirm yellow fever. Together with clinical symptoms, the detection of IgM or a four-fold increase in IgG titer is considered sufficient indication for yellow fever. As these tests can cross-react with other flaviviruses, such as dengue virus, these indirect methods cannot conclusively prove yellow fever infection.Liver biopsy can verify inflammation and necrosis of hepatocytes and detect viral antigens. Because of the bleeding tendency of yellow fever patients, a biopsy is only advisable post mortem to confirm the cause of death.In a differential diagnosis, infections with yellow fever must be distinguished from other feverish illnesses such as malaria. Other viral hemorrhagic fevers, such as Ebola virus, Lassa virus, Marburg virus, and Junin virus, must be excluded as the cause.

Prevention
Personal prevention of yellow fever includes vaccination and avoidance of mosquito bites in areas where yellow fever is endemic. Institutional measures for prevention of yellow fever include vaccination programmes and measures to control mosquitoes. Programmes for distribution of mosquito nets for use in homes produce reductions in cases of both malaria and yellow fever. Use of EPA-registered insect repellent is recommended when outdoors. Exposure for even a short time is enough for a potential mosquito bite. Long-sleeved clothing, long pants, and socks are useful for prevention. The application of larvicides to water-storage containers can help eliminate potential mosquito breeding sites. EPA-registered insecticide spray decreases the transmission of yellow fever.
Use insect repellent when outdoors such as those containing DEET, picaridin, ethyl butylacetylaminopropionate (IR3535), or oil of lemon eucalyptus on exposed skin.
Mosquitoes may bite through thin clothing, so spraying clothes with repellent containing permethrin or another EPA-registered repellent gives extra protection. Clothing treated with permethrin is commercially available. Mosquito repellents containing permethrin are not approved for application directly to the skin.
The peak biting times for many mosquito species are dusk to dawn. However, A. aegypti, one of the mosquitoes that transmits yellow fever virus, feeds during the daytime. Staying in accommodations with screened or air-conditioned rooms, particularly during peak biting times, also reduces the risk of mosquito bites.

Vaccination
Vaccination is recommended for those traveling to affected areas, because non-native people tend to develop more severe illness when infected. Protection begins by the 10th day after vaccine administration in 95% of people, and had been reported to last for at least 10 years. The World Health Organization (WHO) now states that a single dose of vaccine is sufficient to confer lifelong immunity against yellow fever disease. The attenuated live vaccine stem 17D was developed in 1937 by Max Theiler. The WHO recommends routine vaccination for people living in affected areas between the 9th and 12th month after birth.Up to one in four people experience fever, aches, and local soreness and redness at the site of injection. In rare cases (less than one in 200,000 to 300,000), the vaccination can cause yellow fever vaccine-associated viscerotropic disease, which is fatal in 60% of cases. It is probably due to the genetic morphology of the immune system. Another possible side effect is an infection of the nervous system, which occurs in one in 200,000 to 300,000 cases, causing yellow fever vaccine-associated neurotropic disease, which can lead to meningoencephalitis and is fatal in less than 5% of cases.The Yellow Fever Initiative, launched by the WHO in 2006, vaccinated more than 105 million people in 14 countries in West Africa. No outbreaks were reported during 2015. The campaign was supported by the GAVI alliance and governmental organizations in Europe and Africa. According to the WHO, mass vaccination cannot eliminate yellow fever because of the vast number of infected mosquitoes in urban areas of the target countries, but it will significantly reduce the number of people infected.Demand for yellow fever vaccine has continued to increase due to the growing number of countries implementing yellow fever vaccination as part of their routine immunization programmes. Recent upsurges in yellow fever outbreaks in Angola (2015), the Democratic Republic of Congo (2016), Uganda (2016), and more recently in Nigeria and Brazil in 2017 have further increased demand, while straining global vaccine supply. Therefore, to vaccinate susceptible populations in preventive mass immunization campaigns during outbreaks, fractional dosing of the vaccine is being considered as a dose-sparing strategy to maximize limited vaccine supplies. Fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose, which has been reconstituted as per manufacturer recommendations. The first practical use of fractional dose yellow fever vaccination was in response to a large yellow fever outbreak in the Democratic Republic of the Congo in mid-2016.In March 2017, the WHO launched a vaccination campaign in Brazil with 3.5 million doses from an emergency stockpile. In March 2017 the WHO recommended vaccination for travellers to certain parts of Brazil. In March 2018, Brazil shifted its policy and announced it planned to vaccinate all 77.5 million currently unvaccinated citizens by April 2019.

Compulsory vaccination
Some countries in Asia are considered to be potentially in danger of yellow fever epidemics, as both mosquitoes with the capability to transmit yellow fever as well as susceptible monkeys are present. The disease does not yet occur in Asia. To prevent introduction of the virus, some countries demand previous vaccination of foreign visitors who have passed through yellow fever areas. Vaccination has to be proved by a vaccination certificate, which is valid 10 days after the vaccination and lasts for 10 years. Although the WHO on 17 May 2013 advised that subsequent booster vaccinations are unnecessary, an older (than 10 years) certificate may not be acceptable at all border posts in all affected countries. A list of the countries that require yellow fever vaccination is published by the WHO. If the vaccination cannot be given for some reason, dispensation may be possible. In this case, an exemption certificate issued by a WHO-approved vaccination center is required. Although 32 of 44 countries where yellow fever occurs endemically do have vaccination programmes, in many of these countries, less than 50% of their population is vaccinated.

Vector control
Control of the yellow fever mosquito A. aegypti is of major importance, especially because the same mosquito can also transmit dengue fever and chikungunya disease. A. aegypti breeds preferentially in water, for example, in installations by inhabitants of areas with precarious drinking water supplies, or in domestic refuse, especially tires, cans, and plastic bottles. These conditions are common in urban areas in developing countries.Two main strategies are employed to reduce A. aegypti populations. One approach is to kill the developing larvae. Measures are taken to reduce the water accumulations in which the larvae develop. Larvicides are used, along with larvae-eating fish and copepods, which reduce the number of larvae. For many years, copepods of the genus Mesocyclops have been used in Vietnam for preventing dengue fever. This eradicated the mosquito vector in several areas. Similar efforts may prove effective against yellow fever. Pyriproxyfen is recommended as a chemical larvicide, mainly because it is safe for humans and effective in small doses.The second strategy is to reduce populations of the adult yellow fever mosquito. Lethal ovitraps can reduce Aedes populations, using lesser amounts of pesticide because it targets the pest directly. Curtains and lids of water tanks can be sprayed with insecticides, but application inside houses is not recommended by the WHO. Insecticide-treated mosquito nets are effective, just as they are against the Anopheles mosquito that carries malaria.

Treatment
As with other Flavivirus infections, no cure is known for yellow fever. Hospitalization is advisable and intensive care may be necessary because of rapid deterioration in some cases. Certain acute treatment methods lack efficacy: passive immunization after the emergence of symptoms is probably without effect; ribavirin and other antiviral drugs, as well as treatment with interferons, are ineffective in yellow fever patients. Symptomatic treatment includes rehydration and pain relief with drugs such as paracetamol (acetaminophen). Acetylsalicylic acid (aspirin). However, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are often avoided because of an increased risk of gastrointestinal bleeding due to their anticoagulant effects.

Epidemiology
Yellow fever is common in tropical and subtropical areas of South America and Africa. Worldwide, about 600 million people live in endemic areas. The WHO estimates 200,000 cases of yellow fever worldwide each year. About 15% of people infected with yellow fever progress to a severe form of the illness, and up to half of those will die, as there is no cure for yellow fever.

Africa
An estimated 90% of yellow fever infections occur on the African continent. In 2016, a large outbreak originated in Angola and spread to neighboring countries before being contained by a massive vaccination campaign. In March and April 2016, 11 imported cases of the Angola genotype in unvaccinated Chinese nationals were reported in China, the first appearance of the disease in Asia in recorded history.Phylogenetic analysis has identified seven genotypes of yellow fever viruses, and they are assumed to be differently adapted to humans and to the vector A. aegypti. Five genotypes (Angola, Central/East Africa, East Africa, West Africa I, and West Africa II) occur only in Africa. West Africa genotype I is found in Nigeria and the surrounding region. West Africa genotype I appears to be especially infectious, as it is often associated with major outbreaks. The three genotypes found outside of Nigeria and Angola occur in areas where outbreaks are rare. Two outbreaks, in Kenya (1992–1993) and Sudan (2003 and 2005), involved the East African genotype, which had remained undetected in the previous 40 years.

South America
In South America, two genotypes have been identified (South American genotypes I and II). Based on phylogenetic analysis these two genotypes appear to have originated in West Africa and were first introduced into Brazil. The date of introduction of the predecessor African genotype which gave rise to the South American genotypes appears to be 1822 (95% confidence interval 1701 to 1911). The historical record shows an outbreak of yellow fever occurred in Recife, Brazil, between 1685 and 1690. The disease seems to have disappeared, with the next outbreak occurring in 1849. It was likely introduced with the trafficking of slaves through the slave trade from Africa. Genotype I has been divided into five subclades, A through E.In late 2016, a large outbreak began in Minas Gerais state of Brazil that was characterized as a sylvan or jungle epizootic. It began as an outbreak in brown howler monkeys, which serve as a sentinel species for yellow fever, that then spread to men working in the jungle. No cases had been transmitted between humans by the A. aegypti mosquito, which can sustain urban outbreaks that can spread rapidly. In April 2017, the sylvan outbreak continued moving toward the Brazilian coast, where most people were unvaccinated. By the end of May the outbreak appeared to be declining after more than 3,000 suspected cases, 758 confirmed and 264 deaths confirmed to be yellow fever. The Health Ministry launched a vaccination campaign and was concerned about spread during the Carnival season in February and March. The CDC issued a Level 2 alert (practice enhanced precautions.)A Bayesian analysis of genotypes I and II has shown that genotype I accounts for virtually all the current infections in Brazil, Colombia, Venezuela, and Trinidad and Tobago, while genotype II accounted for all cases in Peru. Genotype I originated in the northern Brazilian region around 1908 (95% highest posterior density interval [HPD]: 1870–1936). Genotype II originated in Peru in 1920 (95% HPD: 1867–1958). The estimated rate of mutation for both genotypes was about 5 × 10−4 substitutions/site/year, similar to that of other RNA viruses.

Asia
The main vector (A. aegypti) also occurs in tropical and subtropical regions of Asia, the Pacific, and Australia, but yellow fever has never occurred there, until jet travel introduced 11 cases from the 2016 Angola and DR Congo yellow fever outbreak in Africa. Proposed explanations include:
That the strains of the mosquito in the east are less able to transmit yellow fever virus.
That immunity is present in the populations because of other diseases caused by related viruses (for example, dengue).
That the disease was never introduced because the shipping trade was insufficient.But none is considered satisfactory. Another proposal is the absence of a slave trade to Asia on the scale of that to the Americas. The trans-Atlantic slave trade probably introduced yellow fever into the Western Hemisphere from Africa.

History
Early history
The evolutionary origins of yellow fever most likely lie in Africa, with transmission of the disease from nonhuman primates to humans. The virus is thought to have originated in East or Central Africa and spread from there to West Africa. As it was endemic in Africa, local populations had developed some immunity to it. When an outbreak of yellow fever would occur in an African community where colonists resided, most Europeans died, while the indigenous Africans usually developed nonlethal symptoms resembling influenza. This phenomenon, in which certain populations develop immunity to yellow fever due to prolonged exposure in their childhood, is known as acquired immunity. The virus, as well as the vector A. aegypti, were probably transferred to North and South America with the trafficking of slaves from Africa, part of the Columbian exchange following European exploration and colonization.The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados. An outbreak was recorded by Spanish colonists in 1648 in the Yucatán Peninsula, where the indigenous Mayan people called the illness xekik ("blood vomit"). In 1685, Brazil suffered its first epidemic in Recife. The first mention of the disease by the name "yellow fever" occurred in 1744.
(John Mitchell) (1805) (Mitchells account of the Yellow Fever in Virginia in 1741–2) Archived 2017-02-23 at the Wayback Machine, The Philadelphia Medical Museum, 1 (1) : 1–20.
(John Mitchell) (1814) "Account of the Yellow fever which prevailed in Virginia in the years 1737, 1741, and 1742, in a letter to the late Cadwallader Colden, Esq. of New York, from the late John Mitchell, M.D.F.R.S. of Virginia," Archived 2017-02-23 at the Wayback Machine American Medical and Philosophical Register, 4 : 181–215. The term "yellow fever" appears on p. 186. On p. 188, Mitchell mentions "… the distemper was what is generally called yellow fever in America". However, on pages 191–192, he states "… I shall consider the cause of the yellowness which is so remarkable in this distemper, as to have given it the name of the Yellow Fever."However, Dr. Mitchell misdiagnosed the disease that he observed and treated, and the disease was probably Weils disease or hepatitis. McNeill argues that the environmental and ecological disruption caused by the introduction of sugar plantations created the conditions for mosquito and viral reproduction, and subsequent outbreaks of yellow fever. Deforestation reduced populations of insectivorous birds and other creatures that fed on mosquitoes and their eggs.

In Colonial times and during the Napoleonic Wars, the West Indies were known as a particularly dangerous posting for soldiers due to yellow fever being endemic in the area. The mortality rate in British garrisons in Jamaica was seven times that of garrisons in Canada, mostly because of yellow fever and other tropical diseases. Both English and French forces posted there were seriously affected by the "yellow jack". Wanting to regain control of the lucrative sugar trade in Saint-Domingue (Hispaniola), and with an eye on regaining Frances New World empire, Napoleon sent an army under the command of his brother-in-law General Charles Leclerc to Saint-Domingue to seize control after a slave revolt. The historian J. R. McNeill asserts that yellow fever accounted for about 35,000 to 45,000 casualties of these forces during the fighting. Only one third of the French troops survived for withdrawal and return to France. Napoleon gave up on the island and his plans for North America, selling the Louisiana Purchase to the US in 1803. In 1804, Haiti proclaimed its independence as the second republic in the Western Hemisphere. Considerable debate exists over whether the number of deaths caused by disease in the Haitian Revolution was exaggerated.Although yellow fever is most prevalent in tropical-like climates, the northern United States were not exempted from the fever. The first outbreak in English-speaking North America occurred in New York City in 1668. English colonists in Philadelphia and the French in the Mississippi River Valley recorded major outbreaks in 1669, as well as additional yellow fever epidemics in Philadelphia, Baltimore, and New York City in the 18th and 19th centuries. The disease traveled along steamboat routes from New Orleans, causing some 100,000–150,000 deaths in total. The yellow fever epidemic of 1793 in Philadelphia, which was then the capital of the United States, resulted in the deaths of several thousand people, more than 9% of the population. One of these deaths was James Hutchinson, a physician helping to treat the population of the city. The national government fled the city to Trenton, New Jersey, including President George Washington.

The southern city of New Orleans was plagued with major epidemics during the 19th century, most notably in 1833 and 1853. A major epidemic occurred in both New Orleans and Shreveport, Louisiana in 1873. Its residents called the disease "yellow jack". Urban epidemics continued in the United States until 1905, with the last outbreak affecting New Orleans.At least 25 major outbreaks took place in the Americas during the 18th and 19th centuries, including particularly serious ones in Cartagena, Chile, in 1741; Cuba in 1762 and 1900; Santo Domingo in 1803; and Memphis, Tennessee, in 1878.In the early nineteenth century, the prevalence of yellow fever in the Caribbean "led to serious health problems" and alarmed the United States Navy as numerous deaths and sickness curtailed naval operations and destroyed morale. One episode began in April 1822 when the frigate USS Macedonian left Boston and became part of Commodore James Biddles West India Squadron. Unbeknownst to all, they were about to embark on a cruise to disaster and their assignment "would prove a cruise through hell". Secretary of the Navy Smith Thompson had assigned the squadron to guard United States merchant shipping and suppress piracy. During their time on deployment from 26 May to 3 August 1822, 76 of the Macedonians officers and men died, including John Cadle, surgeon USN. Seventy-four of these deaths were attributed to yellow fever. Biddle reported that another 52 of his crew were on sick-list. In their report to the secretary of the Navy, Biddle and Surgeons Mate Charles Chase stated the cause as "fever". As a consequence of this loss, Biddle noted that his squadron was forced to return to Norfolk Navy Yard early. Upon arrival, the Macedonians crew were provided medical care and quarantined at Craney Island, Virginia.

In 1853, Cloutierville, Louisiana, had a late-summer outbreak of yellow fever that quickly killed 68 of the 91 inhabitants. A local doctor concluded that some unspecified infectious agent had arrived in a package from New Orleans. In 1854, 650 residents of Savannah, Georgia, died from yellow fever. In 1858, St. Matthews German Evangelical Lutheran Church in Charleston, South Carolina, had 308 yellow fever deaths, reducing the congregation by half. A ship carrying persons infected with the virus arrived in Hampton Roads in southeastern Virginia in June 1855. The disease spread quickly through the community, eventually killing over 3,000 people, mostly residents of Norfolk and Portsmouth. In 1873, Shreveport, Louisiana, lost 759 citizens in an 80-day period to a yellow fever epidemic, with over 400 additional victims eventually succumbing. The total death toll from August through November was approximately 1,200.In 1878, about 20,000 people died in a widespread epidemic in the Mississippi River Valley. That year, Memphis had an unusually large amount of rain, which led to an increase in the mosquito population. The result was a huge epidemic of yellow fever. The steamship John D. Porter took people fleeing Memphis northward in hopes of escaping the disease, but passengers were not allowed to disembark due to concerns of spreading yellow fever. The ship roamed the Mississippi River for the next two months before unloading her passengers.Major outbreaks have also occurred in southern Europe. Gibraltar lost many lives to outbreaks in 1804, 1814, and 1828. Barcelona suffered the loss of several thousand citizens during an outbreak in 1821. The Duke de Richelieu deployed 30,000 French troops to the border between France and Spain in the Pyrenees Mountains, to establish a cordon sanitaire in order to prevent the epidemic from spreading from Spain into France.

Causes and transmission
Ezekiel Stone Wiggins, known as the Ottawa Prophet, proposed that the cause of a yellow fever epidemic in Jacksonville, Florida, in 1888, was astrological.
The planets were in the same line as the sun and earth and this produced, besides Cyclones, Earthquakes, etc., a denser atmosphere holding more carbon and creating microbes. Mars had an uncommonly dense atmosphere, but its inhabitants were probably protected from the fever by their newly discovered canals, which were perhaps made to absorb carbon and prevent the disease.
In 1848, Josiah C. Nott suggested that yellow fever was spread by insects such as moths or mosquitoes, basing his ideas on the pattern of transmission of the disease. Carlos Finlay, a Cuban doctor and scientist, proposed in 1881 that yellow fever might be transmitted by previously infected mosquitoes rather than by direct contact from person to person, as had long been believed. Since the losses from yellow fever in the Spanish–American War in the 1890s were extremely high, Army doctors began research experiments with a team led by Walter Reed, and composed of doctors James Carroll, Aristides Agramonte, and Jesse William Lazear. They successfully proved Finlays "mosquito hypothesis". Yellow fever was the first virus shown to be transmitted by mosquitoes. The physician William Gorgas applied these insights and eradicated yellow fever from Havana. He also campaigned against yellow fever during the construction of the Panama Canal. A previous effort of canal building by the French had failed in part due to mortality from the high incidence of yellow fever and malaria, which killed many workers.Although Reed has received much of the credit in United States history books for "beating" yellow fever, he had fully credited Finlay with the discovery of the yellow fever vector, and how it might be controlled. Reed often cited Finlays papers in his own articles, and also credited him for the discovery in his personal correspondence. The acceptance of Finlays work was one of the most important and far-reaching effects of the U.S. Army Yellow Fever Commission of 1900. Applying methods first suggested by Finlay, the United States government and Army eradicated yellow fever in Cuba and later in Panama, allowing completion of the Panama Canal. While Reed built on the research of Finlay, historian François Delaporte notes that yellow fever research was a contentious issue. Scientists, including Finlay and Reed, became successful by building on the work of less prominent scientists, without always giving them the credit they were due. Reeds research was essential in the fight against yellow fever. He is also credited for using the first type of medical consent form during his experiments in Cuba, an attempt to ensure that participants knew they were taking a risk by being part of testing.Like Cuba and Panama, Brazil also led a highly successful sanitation campaign against mosquitoes and yellow fever. Beginning in 1903, the campaign led by Oswaldo Cruz, then director general of public health, resulted not only in eradicating the disease but also in reshaping the physical landscape of Brazilian cities such as Rio de Janeiro. During rainy seasons, Rio de Janeiro had regularly suffered floods, as water from the bay surrounding the city overflowed into Rios narrow streets. Coupled with the poor drainage systems found throughout Rio, this created swampy conditions in the citys neighborhoods. Pools of stagnant water stood year-long in city streets and proved to be a fertile ground for disease-carrying mosquitoes. Thus, under Cruzs direction, public health units known as "mosquito inspectors" fiercely worked to combat yellow fever throughout Rio by spraying, exterminating rats, improving drainage, and destroying unsanitary housing. Ultimately, the citys sanitation and renovation campaigns reshaped Rio de Janeiros neighborhoods. Its poor residents were pushed from city centers to Rios suburbs, or to towns found in the outskirts of the city. In later years, Rios most impoverished inhabitants would come to reside in favelas.

During 1920–1923, the Rockefeller Foundations International Health Board  undertook an expensive and successful yellow fever eradication campaign in Mexico. The IHB gained the respect of Mexicos federal government because of the success. The eradication of yellow fever strengthened the relationship between the US and Mexico, which had not been very good in the years prior. The eradication of yellow fever was also a major step toward better global health.In 1927, scientists isolated the yellow fever virus in West Africa. Following this, two vaccines were developed in the 1930s. Max Theiler led the completion of the 17D yellow fever vaccine in 1937, for which he was subsequently awarded the Nobel Prize in Physiology or Medicine. That vaccine, 17D, is still in use, although newer vaccines, based on vero cells, are in development (as of 2018).

Current status
Using vector control and strict vaccination programs, the urban cycle of yellow fever was nearly eradicated from South America. Since 1943, only a single urban outbreak in Santa Cruz de la Sierra, Bolivia, has occurred. Since the 1980s, however, the number of yellow fever cases has been increasing again, and A. aegypti has returned to the urban centers of South America. This is partly due to limitations on available insecticides, as well as habitat dislocations caused by climate change. It is also because the vector control program was abandoned. Although no new urban cycle has yet been established, scientists believe this could happen again at any point. An outbreak in Paraguay in 2008 was thought to be urban in nature, but this ultimately proved not to be the case.In Africa, virus eradication programs have mostly relied upon vaccination. These programs have largely been unsuccessful because they were unable to break the sylvatic cycle involving wild primates. With few countries establishing regular vaccination programs, measures to fight yellow fever have been neglected, making the future spread of the virus more likely.

Research
In the hamster model of yellow fever, early administration of the antiviral ribavirin is an effective treatment of many pathological features of the disease. Ribavirin treatment during the first five days after virus infection improved survival rates, reduced tissue damage in the liver and spleen, prevented hepatocellular steatosis, and normalised levels of alanine aminotransferase, a liver damage marker. The mechanism of action of ribavirin in reducing liver pathology in yellow fever virus infection may be similar to its activity in treatment of hepatitis C, a related virus </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Animal bite and explain in detail? [/INST] An animal bite is a wound, usually a puncture or laceration, caused by the teeth. An animal bite usually results in a break in the skin but also includes contusions from the excessive pressure on body tissue from the bite. The contusions can occur without a break in the skin. Bites can be provoked or unprovoked. Other bite attacks may be apparently unprovoked.  Biting is a physical action not only describing an attack but it is a normal response in an animal as it eats, carries objects, softens and prepares food for its young, removes ectoparasites from its body surface, removes plant seeds attached to its fur or hair, scratching itself, and grooming other animals. Animal bites often result in serious infections and mortality. Animal bites not only include injuries from the teeth of reptiles, mammals, but fish, and amphibians. Arthropods can also bite and leave injuries.

Signs and symptoms
Bite wounds can cause a number of signs and symptoms

Generalized tissue damage due to tearing and scratching
Serious hemorrhage if major blood vessels are pierced
Infection by bacteria or other pathogens, including rabies
Introduction of venom into the wound by venomous animals such as some snakes
Introduction of other irritants into the wound, causing inflammation and itching

Classification
Bites are usually classified by the type of animal causing the wound.
Many different animals are known to bite humans.

Vertebrates
Companion animals, including dogs, cats, rats, ferrets, and parrots, may bite humans.
Wildlife may sometimes bite humans. The bites of various mammals such as bats, skunks, wolves, raccoons, etc. may transmit rabies, which is almost always fatal if left untreated.
Human bites are themselves capable of doing great flesh damage, but are particularly known for spreading communicable diseasesInvoluntary biting injuries due to closed-fist injuries from fists striking teeth (referred to as reverse bite injuries) are a common consequence of fist fights. These have been termed "fight bites". Injuries in which the knuckle joints or tendons of the hand are bitten into tend to be the most serious.
Teething infants are known to bite objects to relieve pressure on their growing teeth, and may inadvertently bite peoples hands or arms while doing so. Young children may also bite people out of anger or misbehaviour, although this is usually corrected early in the childs life.

Reverse bite injury
A reverse bite injury (also called a clenched fist injury, closed fist injury, or fight bite) results when a person punches another person in the face, and the skin (and sometimes tendons) of their knuckles are cut against the teeth of the person they are punching. The proximity of the wound is often located over the metacarpophalangeal joint resulting in tendon injury.The medical treatment of this injury is similar to those of a human bite, but may also involve damage of the underlying tendons.These injuries should be managed as other human bites: wound irrigation and antibiotics are essential as human saliva can contain a number of bacteria. The nature of these injuries is such that even if the injury is optimally managed, poor outcomes may still occur.

Arthropods
The bites of arthropods have some of the most serious health consequences known. Mosquito bites transmit serious disease and result in millions of deaths and illnesses in the world. Ticks also transmit many diseases such as Lyme disease.

Spider bite
Insect bites and stings
Flea bites are responsible for the transmission of plague.
Mosquito bites are responsible for the transmission of dengue fever and malaria.
Leech bite

Mechanism
Trauma
A natural consequence of a bite is tissue trauma at the site. Trauma may consist of scratching, tearing, punture or laceration of the skin, hematoma (bruising), embedding of foreign objects, for example a tooth or hair, damage to or severing of underlying structures such as connective tissue or muscle, amputations, and the ripping off of skin and hair. If major blood vessels are damaged, severe blood loss can occur.

Infection
Pathogen organisms can be introduced into the bite. Some of the pathogens can originate from the mouth of the biter, the substrate onto which the injured person or animal can fall or from the naturally occurring microorganisms that are present on the skin or hair of the animal. The advent of antibiotics improved the outcome of bite wound infections.

Rabies
Animal bites where skin has been penetrated, most commonly by dogs and bats, transmit rabies to humans. Rabies from other animals is rare. If the animal is caught alive or dead with its head preserved, the head can be analyzed to detect the disease. Signs of rabies include foaming at the mouth, growling, self-mutilation, jerky behavior, red eyes, and hydrophobia.
If the animal cannot be captured, preventative rabies treatment is recommended in many places. Several countries are known not to have native rabies, see the Wikipedia page for prevalence of rabies.

Treatment
The first step in treatment includes washing the bite wound. If there is a low risk of infection the wound may be sutured. Debridement and drainage of bite wounds was practiced in the pre-antibiotic era, but high rates of infection still occurred. A 2019 Cochrane systematic review aimed to evaluate the healing and infection rates in bite wounds based on if/when they were stitched closed. The review authors looked for studies that compared stitching wounds closed straight away, leaving them open for a short time or not stitching them at all. Due to a lack of high-certainty evidence, the review authors concluded that more robust randomised controlled trials were needed to fully answer this question.

Antibiotics
Antibiotics to prevent infection are recommended for dog and cat bites of the hand, and human bites if they are more than superficial. They are also recommended in those who have poor immune function. Evidence for antibiotics to prevent infection in bites in other areas is not clear.The first choice is amoxicillin with clavulanic acid, and if the person is penicillin-allergic, doxycycline and metronidazole. The antistaphylococcal penicillins (e.g., cloxacillin, nafcillin, flucloxacillin) and the macrolides (e.g., erythromycin, clarithromycin) are not used for empirical therapy, because they do not cover Pasteurella species.

Vaccinations
Rabies prevention is generally available in North America and the Northern European states.
Tetanus toxoid treatment is recommended in those whose vaccinations are not up to date and have a bite that punctures the skin. Tetanus immune globulin is indicated in people with more than 10 years since prior vaccination. Tetanus boosters (Td) should be given every ten years.

TT = tetanus toxoid; TIG: tetanus immune globulin

Mosquito bites
Antihistamines are effective treatment for the symptoms from bites. Many diseases such as malaria and dengue are transmitted by mosquitoes.

Epidemiology
Human bites are the third most frequent type of bite after dog and cat bites. Dog bites are commonplace, with children the most commonly bitten and the face and scalp the most common target. About 4.7 million dog bites are reported annually in the United States. The US estimated annual count of animal bites is 250,000 human bites, 1 to 2 million dog bites, 400,000 cat bites, and 45,000 bites from snakes. Bites from skunks, horses, squirrels, rats, rabbits, pigs, and monkeys may be up to 1 percent of bite injuries. Pet ferrets attacks that were unprovoked have caused serious facial injuries. Non-domesticated animals though assumed to be more common especially as a cause of rabies infection, make up less than one percent of reported bite wounds. When a person is bitten, it is more likely to occur on the right arm, most likely due to defensive reactions when the person uses their dominant arm. Estimates are that three-quarters of bites are located on the arms or legs of humans. Bites to the face of humans constitute only 10 percent of the total. Two-thirds of bite injuries in humans are suffered by children aged ten and younger.Up to three-fourths of dog bites happen to those younger than 20 years-old. In the United States, the costs associated with dog bites are estimated to be more than $1 billion annually </s>