<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Pectus excavatum and can you explain it in depth? [/INST] Pectus excavatum is a structural deformity of the anterior thoracic wall in which the sternum and rib cage are shaped abnormally. This produces a caved-in or sunken appearance of the chest. It can either be present at birth or develop after puberty.
Pectus excavatum can impair cardiac and respiratory function and cause pain in the chest and back.
People with the condition may experience severe negative psychosocial effects and avoid activities that expose the chest.

Signs and symptoms
The hallmark of the condition is a sunken appearance of the sternum. The most common form is a cup-shaped concavity, involving the lower end of the sternum; a broader concavity involving the upper costal cartilages is possible. The lower-most ribs may protrude ("flared ribs"). Pectus excavatum defects may be symmetric or asymmetric.
People may also experience chest and back pain, which is usually of musculoskeletal origin.In mild cases, cardiorespiratory function is normal, although the heart can be displaced and/or rotated.  In severe cases, the right atrium may be compressed, mitral valve prolapse may be present, and physical capability may be limited due to base lung capacity being decreased.Psychological symptoms manifest with feelings of embarrassment, social anxiety, shame, limited capacity for activities and communication, negativity, intolerance, frustration, and even depression.

Causes
Researchers are unsure of the cause of pectus excavatum. Some researchers take the stance that it is a congenital disorder (birth defect), but not genetic. Others assume that there is some genetic component. A small sample size test found that in at least some cases, 37% of individuals have an affected first degree family member. As of 2012, a number of genetic markers for pectus excavatum have also been discovered.It was believed for decades that pectus excavatum is caused by an overgrowth of costal cartilage, however people with pectus excavatum actually tend to have shorter, not longer, costal cartilage relative to rib length.Pectus excavatum can be present in other conditions too, including Noonan syndrome, Marfan syndrome and Loeys–Dietz syndrome as well as other connective tissue disorders such as Ehlers–Danlos syndrome. Many children with spinal muscular atrophy develop pectus excavatum due to their diaphragmatic breathing.

Pathophysiology
Physiologically, increased pressure in utero, rickets and increased traction on the sternum due to abnormalities of the diaphragm have been postulated as specific mechanisms. Because the heart is located behind the sternum, and because individuals with pectus excavatum have been shown to have visible deformities of the heart seen both on radiological imaging and after autopsies, it has been hypothesized that there is impairment of the function of the cardiovascular system in individuals with pectus excavatum. While some studies have demonstrated decreased cardiovascular function, no consensus has been reached based on newer physiological tests such as echocardiography of the presence or degree of impairment in cardiovascular function. However, a 2016 meta-analysis found significant evidence that surgical correction of pectus excavatum improves patient cardiac performance.

Diagnosis
Pectus excavatum is initially suspected from visual examination of the anterior chest. Auscultation of the chest can reveal displaced heart beat and valve prolapse. There can be a heart murmur occurring during systole caused by proximity between the sternum and the pulmonary artery.
Lung sounds are usually clear yet diminished due to decreased base lung capacity.Many scales have been developed to determine the degree of deformity in the chest wall. Most of these are variants on the distance between the sternum and the spine. One such index is the Backer ratio which grades severity of deformity based on the ratio between the diameter of the vertebral body nearest to xiphosternal junction and the distance between the xiphosternal junction and the nearest vertebral body. More recently the Haller index has been used based on CT scan measurements. An index over 3.25 is often defined as severe. The Haller index is the ratio between the horizontal distance of the inside of the ribcage and the shortest distance between the vertebrae and sternum.

Chest x-rays are also useful in the diagnosis. The chest x-ray in pectus excavatum can show an opacity in the right lung area that can be mistaken for an infiltrate (such as that seen with pneumonia). Some studies also suggest that the Haller index can be calculated based on chest x-ray as opposed to CT scanning in individuals who have no limitation in their function.Pectus excavatum is differentiated from other disorders by a series of elimination of signs and symptoms. Pectus carinatum is excluded by the simple observation of a collapsing of the sternum rather than a protrusion. Kyphoscoliosis is excluded by diagnostic imaging of the spine, wherein pectus excavatum the spine usually appears normal in structure.

Treatment
Pectus excavatum requires no corrective procedures in mild cases.  Treatment of severe cases can involve either invasive or non-invasive techniques or a combination of both. Before an operation proceeds several tests are usually performed. These include, but are not limited to, a CT scan, pulmonary function tests, and cardiology exams (such as auscultation and ECGs).  After a CT scan is taken, the Haller index is measured. The patients Haller is calculated by obtaining the ratio of the transverse diameter (the horizontal distance of the inside of the ribcage) and the anteroposterior diameter (the shortest distance between the vertebrae and sternum). A Haller Index of greater than 3.25 is generally considered severe, while normal chest has an index of 2.5. The cardiopulmonary tests are used to determine the lung capacity and to check for heart murmurs.

Conservative treatment
The chest wall is elastic, gradually stiffening with age. Non-surgical treatments have been developed that aim at gradually alleviating the pectus excavatum condition, making use of the elasticity of the chest wall, including the costal cartilages, in particular in young cases.

Exercise
Physical exercise  has an important role in conservative pectus excavatum treatment though is not seen as a means to resolve the condition on its own. It is used in order to halt or slow the progression of mild or moderate excavatum conditions and as supplementary treatment to improve a poor posture, to prevent secondary complications, and to prevent relapse after treatment.Exercises are aimed at improving posture, strengthening back and chest muscles, and enhancing exercise capacity, ideally also increasing chest expansion. Pectus exercises include deep breathing and breath holding exercises, as well as strength training for the back and chest muscles. Additionally, aerobic exercises to improve cardiopulmonary function are employed.

Vacuum bell
An alternative to surgery, the vacuum bell, was described in 2006; the procedure is also referred to as treatment by cup suction. It consists of a bowl shaped device which fits over the caved-in area; the air is then removed by the use of a hand pump. The vacuum created by this lifts the sternum upwards, lessening the severity of the deformity. It has been proposed as an alternative to surgery in less severe cases. Once the defect visually disappears, two additional years of use of the vacuum bell is required to make what may be a permanent correction. The treatment, in combination with physiotherapy exercises, has been judged by some as "a promising useful alternative" to surgery provided the thorax is flexible; the duration of treatment that is required has been found to be "directly linked to age, severity and the frequency of use". Long-term results are still lacking.A single-center study reported in the Journal of Pediatric Surgery found that use of vacuum bell therapy resulted in an excellent correction in twenty percent of patients, but "is not a substitute for the Nuss procedure which can achieve an excellent result in 90% of patients". Variables predictive of an excellent outcome include age ≤ 11 years, chest wall depth ≤ 1.5 cm, chest wall flexibility, and vacuum bell use over 12 consecutive months.In an article by Interactive Cardiovascular and Thoracic Surgery, the results found that vacuum bell treatment is safe for correcting the deformity non-surgically. The treatment has been shown to have higher success rates in patients who present earlier, have a mild and/or symmetrical deformity, a flexible chest wall and lack of costal flaring.The vacuum bell can also be used in preparation to surgery.

Orthoses
Brazilian orthopedist Sydney Haje developed a non-surgical protocol for treating pectus carinatum as well as pectus excavatum. The method involves wearing a compressive orthosis and adhering to an exercise protocol.Mild cases have also reportedly been treated with corset-like orthopedic support vests and exercise.

Thoracic surgery
There has been controversy as to the best surgical approach for correction of pectus excavatum. It is important for the surgeon to select the appropriate operative approach based on each individuals characteristics.
Surgical correction has been shown to repair any functional symptoms that may occur in the condition, such as respiratory problems or heart murmurs, provided that permanent damage has not already arisen from an extremely severe case. Surgical correction of the pectus excavatum has been shown to significantly improve cardiovascular function; there is inconclusive evidence so far as to whether it might also improve pulmonary function. One of the most popular techniques for repair of pectus excavatum today is the minimally invasive operation, also known as MIRPE or Nuss technique.

Magnetic mini-mover procedure
The magnetic mini-mover procedure (3MP) is a minimally invasive procedure used to correct pectus excavatum by using two magnets to realign the sternum with the rest of the chest and ribcage. One magnet is inserted 1 cm into the patients body on the lower end of the sternum, the other is placed externally onto a custom fitted brace. These two magnets generate around 0.04 tesla (T) in order to slowly move the sternum outwards over a number of years. The maximum magnetic field that can be applied to the body safely is around 4 T, making this technique safe from a magnetic viewpoint. The 3MP techniques main advantages are that it is more cost-effective than major surgical approaches such as the Nuss procedure and it is considerably less painful postoperatively.
Its effectiveness is limited to younger children in early- to mid-puberty because older individuals have less compliant (flexible) chest walls. One potential adverse interaction with other medical devices is possible inactivation of artificial pacemakers if present.

Ravitch technique
The Ravitch technique is an invasive surgery that was introduced in 1949 and developed in the 1950s. It involves creating an incision along the chest through which the cartilage is removed and the sternum detached. A small bar is inserted underneath the sternum to hold it up in the desired position. The bar is left implanted until the cartilage grows back, typically about six months. The bar is subsequently removed in a simple outpatient procedure; this technique is thus a two-stage procedure.The Ravitch technique is not widely practiced because it is so invasive. It is more often used in older individuals, where the sternum has calcified when the deformity is asymmetrical, or when the less invasive Nuss procedure has proven unsuccessful.

Nuss procedure
In 1987, Donald Nuss, based at Childrens Hospital of The Kings Daughters in Norfolk, Virginia, performed the first minimally invasive repair of pectus excavatum (MIRPE)  and presented it much later at a conference in 1997.His procedure, widely known as the Nuss procedure, involves slipping in one or more concave steel bars into the chest, underneath the sternum. The bar is flipped to a convex position so as to push outward on the sternum, correcting the deformity. The bar usually stays in the body for about two years, although many surgeons are now moving toward leaving them in for up to five years. When the bones have solidified into place, the bar is removed through outpatient surgery. Although initially designed to be performed in younger children (less than 10 years of age) whose sternum and cartilage is more flexible, there are successful series of Nuss treatment in patients well into their teens and twenties.
The Nuss procedure is a two-stage procedure.

Robicsek technique
In 1965, Francis Robicsek, based at Charlotte Memorial Hospital, now named Carolinas Medical Center in Charlotte, North Carolina, developed the Robicsek procedure. Each time the procedure is performed, it is individually tailored based on the extent and location of the deformity in the patient. The operation begins with an incision, no more than 4–6 centimeters, to the sternum. The pectoralis major muscles are then detached from the sternum.  Using the upper limit of the sternal depression as a guide, the deformed cartilages are removed one by one, using sharp and blunt dissection. The lower tip of the sternum is then grabbed with a towel-clip and, using blunt dissection, is freed of tissue connections with the pericardium and the pleura. The sternum is then forcefully bent forward into a corrected position.   To keep the sternum elevated, a piece of mesh is placed under the mobilized sternum and sutured under moderate tension bilaterally to the stumps of the ribs. The pectoralis muscles are united in front of the sternum and the wound is closed. The Robicsek procedure is a single-stage procedure (one surgery only).The purported advantage of this technique is that it is less invasive than the Ravitch technique, but critics have suggested that the relapse rate may be high due to cartilage and bone displaying memory phenomenon.

Taulinoplasty
In 2016, Carlos Bardají, a Barcelona-based pediatric surgeon, together with Lluís Cassou, a biomedical engineer, published a paper describing an extra-thoracic surgical procedure for the correction of pectus excavatum called taulinoplasty. A specially designed implant and traction hardware were developed specifically for the procedure.
In taulinoplasty, a small hole is drilled into the sternum at the deepest point of defect, and a double screw is driven into the hole. Then, a stainless steel implant is placed underneath the skin on top of the sternum and ribs, centered over the double screw. Traction tools are then used to lift the sternum up by the double screw using the implant and ribs for traction. Additional screws are then used to secure the implant onto the sternum holding the sternum in the desired position. Optionally, stainless steel wire may be wrapped around the implant and ribs to further secure the implant in place.
Like the Nuss procedure, taulinoplasty requires follow-up surgery several years later to remove the implanted hardware once the sternum has permanently assumed its new position.
The implant and related hardware used in taulinoplasty is a proprietary product of Ventura Medical Technologies and is marketed as a surgical kit under the brand name Pectus UP.Taulinoplasty was developed to be an alternative to the Nuss procedure that eliminates the risks and drawbacks of entering the thorax. In particular, patients usually have shorter operating and recovery times, and less post-operative pain than with the Nuss procedure.

Plastic surgery
Implants
The implant allows pectus excavatum to be treated from a purely morphological perspective. Today it is used as a benchmark procedure as it is simple, reliable, and minimally intrusive while offering aesthetically pleasing results. This procedure does not, however, claim to correct existing cardiac and respiratory problems which, in very rare cases, can be triggered by the pectus excavatum condition. For female patients, the potential resulting breast asymmetry can be partially or completely corrected by this procedure.The process of creating a plaster-cast model, directly on the skin of the patients thorax, can be used in the design of the implants. The evolution of medical imaging and CAD (computer-aided design) now allows customised 3D implants to be designed directly from the ribcage, therefore being much more precise, easier to place sub-pectorally and perfectly adapted to the shape of each patient. The implants are made of medical silicon rubber which is age-resistant and unbreakable (different to the silicon gel used in breast implants). They will last for life (apart from the case of adverse reactions) and are not visible externally.
The surgery is performed under general anesthesia and takes about an hour. The surgeon makes an incision of approximately seven centimetres, prepares the customised space in the chest, inserts the implant deep beneath the muscle, then closes the incision. Post-operative hospitalization is typically around three days.The recovery after the surgery typically requires only mild pain relief. Post-operatively, a surgical dressing is required for several days and compression vest for a month following the procedure. A check-up appointment is carried out after a week for puncture of seroma. If the surgery has minimal complications, the patient can resume normal activities quickly, returning to work after 15 days and participating in any sporting activities after three months.

Lipofilling
The "lipofilling" technique consists of sucking fat from the patient using a syringe with a large gauge needle (usually from the abdomen or the outer thighs), then after centrifugation, the fat cells are re-injected beneath the skin into whichever hollow it is needed to fill. This technique is primarily used to correct small defects which may persist after conventional surgical treatment.

Epidemiology
Pectus excavatum occurs in an estimated 1 in 150 to 1 in 1000 births, with male predominance (male-to-female ratio of 3:1). In 35% to 45% of cases family members are affected.

Etymology
Pectus excavatum is from Latin meaning hollowed chest.  It is sometimes referred to as sunken chest syndrome, cobblers chest or funnel chest.

Society
American Olympic swimmer Cody Miller (born 1992) opted not to have treatment for pectus excavatum, even though it limited his lung capacity. He earned a gold medal in 2016.
Actor Joel Kinnaman underwent surgery prior to the filming of Altered Carbon, inserting two metal bars to push the sternum outward in order to correct the deformity. English comedian and presenter Josh Widdicombe and YouTuber/streamer Ludwig Ahgren are known to have this condition. Zachary Woods is another popular American actor that has pectus excavatum, which is noticeable in his shirtless scene in an episode of The Office (Season 8, episode 12).

In animals
Pectus excavatum is also known to occur in animals, e.g. the Munchkin breed of cat. Some procedures used to treat the condition in animals have not been used in human treatments, such as the use of a cast with sutures wrapped around the sternum and the use of internal and external splints. These techniques are generally used in immature animals with flexible cartilage.

See also
Pectus carinatum

References
Further reading
Tocchioni F, Ghionzoli M, Messineo A, Romagnoli P (2013). "Pectus excavatum and heritable disorders of the connective tissue" </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Childhood disintegrative disorder and can you explain it in depth? [/INST] Childhood disintegrative disorder (CDD), also known as Hellers syndrome and disintegrative psychosis, is a rare condition characterized by late onset of developmental delays—or severe and sudden reversals—in language, social function, and motor skills. Researchers have not been successful in finding a cause for the disorder. CDD has some similarity to autism and is sometimes considered a low-functioning form of it. In May 2013, CDD, along with other sub-types of PDD (Aspergers syndrome, autism, and PDD-NOS), was fused into a single diagnostic term called "autism spectrum disorder" under the new DSM-5 manual.CDD was originally described by Austrian educator Theodor Heller (1869–1938) in 1908, 35 years before Leo Kanner and Hans Asperger described autism. Heller had previously used the name dementia infantilis for the syndrome.An apparent period of fairly normal development is often noted before a regression in skills or a series of regressions in skills. The age at which this regression can occur varies, after three years of normal development is typical. The regression, known as a ‘prodrome,’ can be so dramatic that the child may be aware of it, and may in its beginning even ask, vocally, what is happening to them. Some children describe or appear to be reacting to hallucinations, but the most obvious symptom is that skills apparently attained are lost.Many children are already somewhat delayed when the disorder becomes apparent, but these delays are not always obvious in young children. This has been described by many writers as a devastating condition, affecting both the family and the individuals future. As is the case with all pervasive developmental disorder categories, there is considerable controversy about the right treatment for CDD.

Signs and symptoms
CDD is a rare condition, with only 1.7 cases per 100,000.A child affected with childhood disintegrative disorder shows normal development. Up until this point, the child has developed normally in the areas of language skills, social skills, comprehension skills, and has maintained those skills for about two years. However, between the ages of two and 10, skills acquired are lost almost completely in at least two of the following six functional areas:
Expressive language skills (being able to produce speech and communicate a message)
Receptive language skills (comprehension of language – listening and understanding what is communicated)
Social skills and self care skills
Control over bowel and bladder
Play skills
Motor skillsLack of normal function or impairment also occurs in at least two of the following three areas:
Social interaction
Communication
Repetitive behavior and interest patternsIn her book, Thinking in Pictures, Temple Grandin argues that compared to "Kanners classic autism" and to Asperger syndrome, CDD is characterized with more severe sensory processing disorder but less severe cognitive problems. She also argues that compared to most autistic individuals, persons with CDD have more severe speech pathology and they usually do not respond well to stimulants.

Causes
All of the causes of childhood disintegrative disorder are still unknown. Sometimes CDD surfaces abruptly within days or weeks, while in other cases it develops over a longer period of time. A Mayo Clinic report indicates: "Comprehensive medical and neurological examinations in children diagnosed with childhood disintegrative disorder seldom uncover an underlying medical or neurological cause. Although the occurrence of epilepsy is higher in children with childhood disintegrative disorder, experts dont know whether epilepsy plays a role in causing the disorder."CDD, especially in cases of later age of onset, has also been associated with certain other conditions, particularly the following:
Lipid storage diseases: In this condition, a toxic buildup of excess fats (lipids) takes place in the brain and nervous system.
Subacute sclerosing panencephalitis: Chronic infection of the brain by a form of the measles virus causes subacute sclerosing panencephalitis. This condition leads to brain inflammation and the death of nerve cells.
Tuberous sclerosis (TSC): TSC is a genetic disorder. In this disorder, tumors may grow in the brain and other vital organs like kidneys, heart, eyes, lungs, and skin. In this condition, noncancerous (benign) tumors, hamartomas, grow in the brain.
 Leukodystrophy: In this condition, the myelin sheath does not develop in a normal way, causing white matter in the brain to eventually fail and disintegrate.

Treatment
Loss of language and skills related to social interaction and self-care are serious. The affected children face ongoing disabilities in certain areas and require long-term care. Treatment of CDD involves both behavior therapy, environmental therapy and medications.
Behavior therapy: Applied Behavior Analysis (ABA) is considered to be the most effective form of treatment for Autism spectrum disorders by the American Academy of Pediatrics. The primary goal of ABA is to improve quality of life, and independence by teaching adaptive behaviors to children with autism, and to diminish problematic behaviors like running away from home, or self-injury by using positive or negative reinforcement to encourage or discourage behaviors over time.
Environmental Therapy: Sensory Enrichment Therapy uses enrichment of the sensory experience to improve symptoms in autism, many of which are common to CDD.
Medications: There are no medications available to directly treat CDD. Antipsychotic medications are used to treat severe behavior problems like aggressive stance and repetitive behavior patterns. Anticonvulsant medications are used to control seizures.

References
Further reading
Maurice, Catherine (1993). Let me hear your voice: a familys triumph over autism. New York: Knopf </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Bubonic plague and can you explain it in depth? [/INST] Bubonic plague is one of three types of plague caused by the plague bacterium (Yersinia pestis). One to seven days after exposure to the bacteria, flu-like symptoms develop. These symptoms include fever, headaches, and vomiting, as well as swollen and painful lymph nodes occurring in the area closest to where the bacteria entered the skin. Acral necrosis, the dark discoloration of skin, is another symptom. Occasionally, swollen lymph nodes, known as "buboes," may break open.The three types of plague are the result of the route of infection: bubonic plague, septicemic plague, and pneumonic plague. Bubonic plague is mainly spread by infected fleas from small animals. It may also result from exposure to the body fluids from a dead plague-infected animal. Mammals such as rabbits, hares, and some cat species are susceptible to bubonic plague, and typically die upon contraction. In the bubonic form of plague, the bacteria enter through the skin through a flea bite and travel via the lymphatic vessels to a lymph node, causing it to swell. Diagnosis is made by finding the bacteria in the blood, sputum, or fluid from lymph nodes.Prevention is through public health measures such as not handling dead animals in areas where plague is common. While vaccines against the plague have been developed, the World Health Organization recommends that only high-risk groups, such as certain laboratory personnel and health care workers, get inoculated. Several antibiotics are effective for treatment, including streptomycin, gentamicin, and doxycycline.Without treatment, plague results in the death of 30% to 90% of those infected. Death, if it occurs, is typically within 10 days. With treatment, the risk of death is around 10%. Globally between 2010 and 2015 there were 3,248 documented cases, which resulted in 584 deaths. The countries with the greatest number of cases are the Democratic Republic of the Congo, Madagascar, and Peru.The plague is considered the likely cause of the Black Death that swept through Asia, Europe, and Africa in the 14th century and killed an estimated 50 million people, including about 25% to 60% of the European population. Because the plague killed so many of the working population, wages rose due to the demand for labor. Some historians see this as a turning point in European economic development. The disease is also considered to have been responsible for the Plague of Justinian, originating in the Eastern Roman Empire in the 6th century CE, as well as the third epidemic, affecting China, Mongolia, and India, originating in the Yunnan Province in 1855. The term bubonic is derived from the Greek word βουβών, meaning "groin".

Cause
Bubonic plague is an infection of the lymphatic system, usually resulting from the bite of an infected flea, Xenopsylla cheopis (the Oriental rat flea). Several flea species carried the bubonic plague, such as Pulex irritans (the human flea), Xenopsylla cheopis, and Ceratophyllus fasciatus. Xenopsylla cheopis was the most effective flea species for transmittal. In very rare circumstances, as in septicemic plague, the disease can be transmitted by direct contact with infected tissue or exposure to the cough of another human. The flea is parasitic on house and field rats and seeks out other prey when its rodent hosts die. Rats were an amplifying factor to bubonic plague due to their common association with humans as well as the nature of their blood. The rats blood allowed the rat to withstand a major concentration of the plague. The bacteria form aggregates in the gut of infected fleas and this results in the flea regurgitating ingested blood, which is now infected, into the bite site of a rodent or human host. Once established, bacteria rapidly spread to the lymph nodes and multiply. The fleas that transmit the disease only directly infect humans when the rat population in the area is wiped out from a mass infection. Furthermore, in areas of a large population of rats, the animals can harbor low levels of the plague infection without causing human outbreaks. With no new rat inputs being added to the population from other areas, the infection would only spread to humans in very rare cases of overcrowding.

Signs and symptoms
After being transmitted via the bite of an infected flea, the Y. pestis bacteria become localized in an inflamed lymph node, where they begin to colonize and reproduce. Infected lymph nodes develop hemorrhages, which result in the death of tissue.Y. pestis bacilli can resist phagocytosis and even reproduce inside phagocytes and kill them. As the disease progresses, the lymph nodes can hemorrhage and become swollen and necrotic. Bubonic plague can progress to lethal septicemic plague in some cases. The plague is also known to spread to the lungs and become the disease known as the pneumonic plague. Symptoms appear 2–7 days after getting bitten and they include:
Chills
General ill feeling (malaise)
High fever >39 °C (102.2 °F)
Muscle cramps
Seizures
Smooth, painful lymph gland swelling called a bubo, commonly found in the groin, but may occur in the armpits or neck, most often near the site of the initial infection (bite or scratch)
Pain may occur in the area before the swelling appears
Gangrene of the extremities such as toes, fingers, lips, and tip of the nose.The best-known symptom of bubonic plague is one or more infected, enlarged, and painful lymph nodes, known as buboes. Buboes associated with the bubonic plague are commonly found in the armpits, upper femoral, groin, and neck region. Symptoms include heavy breathing, continuous vomiting of blood (hematemesis), aching limbs, coughing, and extreme pain caused by the decay or decomposition of the skin while the person is still alive. Additional symptoms include extreme fatigue, gastrointestinal problems, spleen inflammation, lenticulae (black dots scattered throughout the body), delirium, coma, organ failure, and death. Organ failure is a result of the bacteria infecting organs through the bloodstream. Other forms of the disease include septicemic plague and pneumonic plague in which the bacterium reproduces in the persons blood and lungs respectively.

Diagnosis
Laboratory testing is required in order to diagnose and confirm plague. Ideally, confirmation is through the identification of Y. pestis culture from a patient sample. Confirmation of infection can be done by examining serum taken during the early and late stages of infection. To quickly screen for the Y. pestis antigen in patients, rapid dipstick tests have been developed for field use. Samples taken for testing include:Buboes: Swollen lymph nodes (buboes) characteristic of bubonic plague, a fluid sample can be taken from them with a needle.
Blood
Lungs

Prevention
Bubonic plague outbreaks are controlled by pest control and modern sanitation techniques. This disease uses fleas commonly found on rats as a vector to jump from animals to humans. The mortality rate hits its peak during the hot and humid months of June, July, and August. Furthermore, the plague most affected those of poor upbringing due to greater exposure, poor sanitation techniques and lack of a healthy immune system due to a poor diet. The successful control of rat populations in dense urban areas is essential to outbreak prevention. One example is the use of a machine called the Sulfurozador, used to deliver sulphur dioxide to eradicate the pest that spread the bubonic plague, in Buenos Aires, Argentina during the early 18th century. Targeted chemoprophylaxis, sanitation, and vector control also played a role in controlling the 2003 Oran outbreak of the bubonic plague. Another means of prevention in large European cities was a city-wide quarantine to not only limit interaction with people who were infected, but also to limit the interaction with the infected rats.

Treatment
Several classes of antibiotics are effective in treating bubonic plague. These include aminoglycosides such as streptomycin and gentamicin, tetracyclines (especially doxycycline), and the fluoroquinolone ciprofloxacin. Mortality associated with treated cases of bubonic plague is about 1–15%, compared to a mortality of 40–60% in untreated cases.People potentially infected with the plague need immediate treatment and should be given antibiotics within 24 hours of the first symptoms to prevent death. Other treatments include oxygen, intravenous fluids, and respiratory support. People who have had contact with anyone infected by pneumonic plague are given prophylactic antibiotics. Using the broad-based antibiotic streptomycin has proven to be dramatically successful against the bubonic plague within 12 hours of infection.

Epidemiology
Globally between 2010 and 2015, there were 3,248 documented cases, which resulted in 584 deaths. The countries with the greatest number of cases are the Democratic Republic of the Congo, Madagascar, and Peru.For over a decade since 2001, Zambia, India, Malawi, Algeria, China, Peru, and the Democratic Republic of the Congo had the most plague cases with over 1,100 cases in the Democratic Republic of the Congo alone. From 1,000 to 2,000 cases are conservatively reported per year to the WHO. From 2012 to 2017, reflecting political unrest and poor hygienic conditions, Madagascar began to host regular epidemics.Between 1900 and 2015, the United States had 1,036 human plague cases with an average of 9 cases per year. In 2015, 16 people in the Western United States developed plague, including 2 cases in Yosemite National Park. These US cases usually occur in rural northern New Mexico, northern Arizona, southern Colorado, California, southern Oregon, and far western Nevada.In November 2017, the Madagascar Ministry of Health reported an outbreak to the WHO (World Health Organization) with more cases and deaths than any recent outbreak in the country. Unusually, most of the cases were pneumonic rather than bubonic.In June 2018, a child was confirmed to be the first person in Idaho to be infected by bubonic plague in nearly 30 years.A couple died in May 2019, in Mongolia, while hunting marmots. Another two people in the province of Inner Mongolia, China were treated in November 2019 for the disease.

In July 2020, in Bayannur, Inner Mongolia of China, a human case of bubonic plague was reported. Officials responded by activating a city-wide plague-prevention system for the remainder of the year. Also in July 2020, in Mongolia, a teenager died from bubonic plague after consuming infected marmot meat.

History
Yersinia pestis has been discovered in archaeological finds from the Late Bronze Age (~3800 BP). The bacteria is identified by ancient DNA in human teeth from Asia and Europe dating from 2,800 to 5,000 years ago.

First pandemic
The first recorded epidemic affected the Sasanian Empire and their arch-rivals, the Eastern Roman Empire (Byzantine Empire) and was named the Plague of Justinian after emperor Justinian I, who was infected but survived through extensive treatment. The pandemic resulted in the deaths of an estimated 25 million (6th century outbreak) to 50 million people (two centuries of recurrence). The historian Procopius wrote, in Volume II of History of the Wars, of his personal encounter with the plague and the effect it had on the rising empire. In the spring of 542, the plague arrived in Constantinople, working its way from port city to port city and spreading around the Mediterranean Sea, later migrating inland eastward into Asia Minor and west into Greece and Italy. The Plague of Justinian is said to have been "completed" in the middle of the 8th century. Because the infectious disease spread inland by the transferring of merchandise through Justinians efforts in acquiring luxurious goods of the time and exporting supplies, his capital became the leading exporter of the bubonic plague. Procopius, in his work Secret History, declared that Justinian was a demon of an emperor who either created the plague himself or was being punished for his sinfulness.

Second pandemic
In the Late Middle Ages Europe experienced the deadliest disease outbreak in history when the Black Death, the infamous pandemic of bubonic plague, hit in 1347, killing one-third of the European human population. Some historians believe that society subsequently became more violent as the mass mortality rate cheapened life and thus increased warfare, crime, popular revolt, waves of flagellants, and persecution. The Black Death originated in Central Asia and spread from Italy and then throughout other European countries. Arab historians Ibn Al-Wardni and Almaqrizi believed the Black Death originated in Mongolia. Chinese records also showed a huge outbreak in Mongolia in the early 1330s.In 2022, researchers presented evidence that the plague originated near Lake Issyk-Kul in Kyrgyzstan. The Mongols had cut the trade route (the Silk Road) between China and Europe, which halted the spread of the Black Death from eastern Russia to Western Europe. The European epidemic began with an attack that Mongols launched on the Italian merchants last trading station in the region, Caffa in the Crimea.In late 1346, plague broke out among the besiegers and from them penetrated the town. The Mongol forces catapulted plague-infested corpses into Caffa as a form of attack, one of the first known instances of biological warfare. When spring arrived, the Italian merchants fled on their ships, unknowingly carrying the Black Death. Carried by the fleas on rats, the plague initially spread to humans near the Black Sea and then outwards to the rest of Europe as a result of people fleeing from one area to another. Rats migrated with humans, traveling among grain bags, clothing, ships, wagons, and grain husks. Continued research indicates that black rats, those that primarily transmitted the disease, prefer grain as a primary meal. Due to this, the major bulk grain fleets that transported major citys food shipments from Africa and Alexandria to heavily populated areas, and were then unloaded by hand, played a role in increasing the transmission effectiveness of the plague.

Third pandemic
The plague resurfaced for a third time in the mid-19th century; this is also known as "the modern pandemic". Like the two previous outbreaks, this one also originated in Eastern Asia, most likely in Yunnan, a province of China, where there are several natural plague foci. The initial outbreaks occurred in the second half of the 18th century. The disease remained localized in Southwest China for several years before spreading. In the city of Canton, beginning in January 1894, the disease had killed 80,000 people by June. Daily water-traffic with the nearby city of Hong Kong rapidly spread the plague there, killing over 2,400 within two months during the 1894 Hong Kong plague.The third pandemic spread the disease to port cities throughout the world in the second half of the 19th century and the early 20th century via shipping routes. The plague infected people in Chinatown in San Francisco from 1900 to 1904, and in the nearby locales of Oakland and the East Bay again from 1907 to 1909. During the former outbreak, in 1902, authorities made permanent the Chinese Exclusion Act, a law originally signed into existence by President Chester A. Arthur in 1882. The Act was supposed to last for 10 years, but was renewed in 1892 with the Geary Act, then followed by the 1902 decision. The last major outbreak in the United States occurred in Los Angeles in 1924, though the disease is still present in wild rodents and can be passed to humans that come in contact with them. According to the World Health Organization, the pandemic was considered active until 1959, when worldwide casualties dropped to 200 per year. In 1994, a plague outbreak in five Indian states caused an estimated 700 infections (including 52 deaths) and triggered a large migration of Indians within India as they tried to avoid the disease.It was during the 1894 Hong Kong plague outbreak that Alexandre Yersin isolated the bacterium responsible (Yersinia pestis), a few days after Japanese bacteriologist Kitasato Shibasaburō had isolated it. However, the latters description was imprecise and also expressed doubts of its relation to the disease, and thus the bacterium is today only named after Yersin.

Society and culture
The scale of death and social upheaval associated with plague outbreaks has made the topic prominent in many historical and fictional accounts since the disease was first recognized. The Black Death in particular is described and referenced in numerous contemporary sources, some of which, including works by Chaucer, Boccaccio, and Petrarch, are considered part of the Western canon. The Decameron, by Boccaccio, is notable for its use of a frame story involving individuals who have fled Florence for a secluded villa to escape the Black Death. First-person, sometimes sensationalized or fictionalized, accounts of living through plague years have also been popular across centuries and cultures. For example, Samuel Pepyss diary makes several references to his first-hand experiences of the Great Plague of London in 1665–6.Later works, such as Albert Camuss novel The Plague or Ingmar Bergmans film The Seventh Seal have used bubonic plague in settings, such as quarantined cities in either medieval or modern times, as a backdrop to explore a variety of concepts. Common themes include the breakdown of society, institutions, and individuals during the plague, the cultural and psychological existential confrontation with mortality, and the allegorical use of the plague about contemporary moral or spiritual questions.

Biological warfare
Some of the earliest instances of biological warfare were said to have been products of the plague, as armies of the 14th century were recorded catapulting diseased corpses over the walls of towns and villages to spread the pestilence. This was done by Jani Beg when he attacked the city of Kaffa in 1343.Later, plague was used during the Second Sino-Japanese War as a bacteriological weapon by the Imperial Japanese Army. These weapons were provided by Shirō Ishiis units and used in experiments on humans before being used on the field. For example, in 1940, the Imperial Japanese Army Air Service bombed Ningbo with fleas carrying the bubonic plague. During the Khabarovsk War Crime Trials, the accused, such as Major General Kiyoshi Kawashima, testified that, in 1941, 40 members of Unit 731 air-dropped plague-contaminated fleas on Changde. These operations caused epidemic plague outbreaks.

Continued research
Substantial research has been done regarding the origin of the plague and how it traveled through the continent </s>


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