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Control engineering

Control engineering or control systems engineering is an engineering discipline that deals with control systems, applying control theory to design equipment and systems with desired behaviors in control environments. The discipline of controls overlaps and is usually taught along with electrical engineering, chemical engineering and mechanical engineering at many institutions around the world.

The practice uses sensors and detectors to measure the output performance of the process being controlled; these measurements are used to provide corrective feedback helping to achieve the desired performance. Systems designed to perform without requiring human input are called automatic control systems (such as cruise control for regulating the speed of a car). Multi-disciplinary in nature, control systems engineering activities focus on implementation of control systems mainly derived by mathematical modeling of a diverse range of systems.

Overview
Modern day control engineering is a relatively new field of study that gained significant attention during the 20th century with the advancement of technology. It can be broadly defined or classified as practical application of control theory. Control engineering plays an essential role in a wide range of control systems, from simple household washing machines to high-performance fighter aircraft. It seeks to understand physical systems, using mathematical modelling, in terms of inputs, outputs and various components with different behaviors; to use control system design tools to develop controllers for those systems; and to implement controllers in physical systems employing available technology. A system can be mechanical, electrical, fluid, chemical, financial or biological, and its mathematical modelling, analysis and controller design uses control theory in one or many of the time, frequency and complex-s domains, depending on the nature of the design problem.

Control engineering is the engineering discipline that focuses on the modeling of a diverse range of dynamic systems (e.g. mechanical systems) and the design of controllers that will cause these systems to behave in the desired manner. Although such controllers need not be electrical, many are and hence control engineering is often viewed as a subfield of electrical engineering.

Electrical circuits, digital signal processors and microcontrollers can all be used to implement control systems. Control engineering has a wide range of applications from the flight and propulsion systems of commercial airliners to the cruise control present in many modern automobiles.

In most cases, control engineers utilize feedback when designing control systems. This is often accomplished using a PID controller system. For example, in an automobile with cruise control the vehicle's speed is continuously monitored and fed back to the system, which adjusts the motor's torque accordingly. Where there is regular feedback, control theory can be used to determine how the system responds to such feedback. In practically all such systems stability is important and control theory can help ensure stability is achieved.

Although feedback is an important aspect of control engineering, control engineers may also work on the control of systems without feedback. This is known as open loop control. A classic example of open loop control is a washing machine that runs through a pre-determined cycle without the use of sensors.

History

Automatic control systems were first developed over two thousand years ago. The first feedback control device on record is thought to be the ancient Ktesibios's water clock in Alexandria, Egypt, around the third century BCE. It kept time by regulating the water level in a vessel and, therefore, the water flow from that vessel. This certainly was a successful device as water clocks of similar design were still being made in Baghdad when the Mongols captured the city in 1258 CE. A variety of automatic devices have been used over the centuries to accomplish useful tasks or simply just to entertain. The latter includes the automata, popular in Europe in the 17th and 18th centuries, featuring dancing figures that would repeat the same task over and over again; these automata are examples of open-loop control. Milestones among feedback, or "closed-loop" automatic control devices, include the temperature regulator of a furnace attributed to Drebbel, circa 1620, and the centrifugal flyball governor used for regulating the speed of steam engines by James Watt in 1788.

In his 1868 paper "On Governors", James Clerk Maxwell was able to explain instabilities exhibited by the flyball governor using differential equations to describe the control system. This demonstrated the importance and usefulness of mathematical models and methods in understanding complex phenomena, and it signaled the beginning of mathematical control and systems theory. Elements of control theory had appeared earlier but not as dramatically and convincingly as in Maxwell's analysis.

Control theory made significant strides over the next century. New mathematical techniques, as well as advances in electronic and computer technologies, made it possible to control significantly more complex dynamical systems than the original flyball governor could stabilize. New mathematical techniques included developments in optimal control in the 1950s and 1960s followed by progress in stochastic, robust, adaptive, nonlinear control methods in the 1970s and 1980s. Applications of control methodology have helped to make possible space travel and communication satellites, safer and more efficient aircraft, cleaner automobile engines, and cleaner and more efficient chemical processes.

Before it emerged as a unique discipline, control engineering was practiced as a part of mechanical engineering and control theory was studied as a part of electrical engineering since electrical circuits can often be easily described using control theory techniques. In the first control relationships, a current output was represented by a voltage control input. However, not having adequate technology to implement electrical control systems, designers were left with the option of less efficient and slow responding mechanical systems. A very effective mechanical controller that is still widely used in some hydro plants is the governor. Later on, previous to modern power electronics, process control systems for industrial applications were devised by mechanical engineers using pneumatic and hydraulic control devices, many of which are still in use today.

Education
At many universities around the world, control engineering courses are taught primarily in electrical engineering and mechanical engineering, but some courses can be instructed in mechatronics engineering, and aerospace engineering. In others, control engineering is connected to computer science, as most control techniques today are implemented through computers, often as embedded systems (as in the automotive field). The field of control within chemical engineering is often known as process control. It deals primarily with the control of variables in a chemical process in a plant. It is taught as part of the undergraduate curriculum of any chemical engineering program and employs many of the same principles in control engineering. Other engineering disciplines also overlap with control engineering as it can be applied to any system for which a suitable model can be derived. However, specialised control engineering departments do exist, for example, in Italy there are several master in Automation & Robotics that are fully specialised in Control engineering or the Department of Automatic Control and Systems Engineering at the University of Sheffield or the Department of Robotics and Control Engineering at the United States Naval Academy and the Department of Control and Automation Engineering at the Istanbul Technical University.

Control engineering has diversified applications that include science, finance management, and even human behavior. Students of control engineering may start with a linear control system course dealing with the time and complex-s domain, which requires a thorough background in elementary mathematics and Laplace transform, called classical control theory. In linear control, the student does frequency and time domain analysis. Digital control and nonlinear control courses require Z transformation and algebra respectively, and could be said to complete a basic control education.

Careers
A control engineer's career starts with a bachelor's degree and can continue through the college process. Control engineer degrees are well paired with an electrical or mechanical engineering degree. Control engineers usually get jobs in technical managing where they typically lead interdisciplinary projects. There are many job opportunities in aerospace companies, manufacturing companies, automobile companies, power companies, and government agencies. Some places that hire Control Engineers include companies such as Rockwell Automation, NASA, Ford, and Goodrich. Control Engineers can possibly earn $66k annually from Lockheed Martin Corp. They can also earn up to $96k annually from General Motors Corporation.

According to a Control Engineering survey, most of the people who answered were control engineers in various forms of their own career. There are not very many careers that are classified as "control engineer", most of them are specific careers that have a small semblance to the overarching career of control engineering. A majority of the control engineers that took the survey in 2019 are system or product designers, or even control or instrument engineers. Most of the jobs involve process engineering or production or even maintenance, they are some variation of control engineering.

Recent advancement
Originally, control engineering was all about continuous systems. Development of computer control tools posed a requirement of discrete control system engineering because the communications between the computer-based digital controller and the physical system are governed by a computer clock. The equivalent to Laplace transform in the discrete domain is the Z-transform. Today, many of the control systems are computer controlled and they consist of both digital and analog components.

Therefore, at the design stage either digital components are mapped into the continuous domain and the design is carried out in the continuous domain, or analog components are mapped into discrete domain and design is carried out there. The first of these two methods is more commonly encountered in practice because many industrial systems have many continuous systems components, including mechanical, fluid, biological and analog electrical components, with a few digital controllers.

Similarly, the design technique has progressed from paper-and-ruler based manual design to computer-aided design and now to computer-automated design or CAD which has been made possible by evolutionary computation. CAD can be applied not just to tuning a predefined control scheme, but also to controller structure optimisation, system identification and invention of novel control systems, based purely upon a performance requirement, independent of any specific control scheme.

Resilient control systems extend the traditional focus of addressing only planned disturbances to frameworks and attempt to address multiple types of unexpected disturbance; in particular, adapting and transforming behaviors of the control system in response to malicious actors, abnormal failure modes, undesirable human action, etc.

title: Control engineering


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Chagas disease

Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by Trypanosoma cruzi. It is spread mostly by insects in the subfamily Triatominae, known as "kissing bugs". The symptoms change over the course of the infection. In the early stage, symptoms are typically either not present or mild, and may include fever, swollen lymph nodes, headaches, or swelling at the site of the bite. After four to eight weeks, untreated individuals enter the chronic phase of disease, which in most cases does not result in further symptoms. Up to 45% of people with chronic infections develop heart disease 10–30 years after the initial illness, which can lead to heart failure. Digestive complications, including an enlarged esophagus or an enlarged colon, may also occur in up to 21% of people, and up to 10% of people may experience nerve damage.

T. cruzi is commonly spread to humans and other mammals by the kissing bug's bite wound and the bug's infected feces. The disease may also be spread through blood transfusion, organ transplantation, consuming food or drink contaminated with the parasites, and vertical transmission (from a mother to her baby). Diagnosis of early disease is by finding the parasite in the blood using a microscope or detecting its DNA by polymerase chain reaction. Chronic disease is diagnosed by finding antibodies for T. cruzi in the blood.

Prevention focuses on eliminating kissing bugs and avoiding their bites. This may involve the use of insecticides or bed-nets. Other preventive efforts include screening blood used for transfusions. Early infections are treatable with the medications benznidazole or nifurtimox, which usually cure the disease if given shortly after the person is infected, but become less effective the longer a person has had Chagas disease. When used in chronic disease, medication may delay or prevent the development of end-stage symptoms. Benznidazole and nifurtimox often cause side effects, including skin disorders, digestive system irritation, and neurological symptoms, which can result in treatment being discontinued. New drugs for Chagas disease are under development, and while experimental vaccines have been studied in animal models, a human vaccine has not been developed.

It is estimated that 6.5 million people, mostly in Mexico, Central America and South America, have Chagas disease as of 2019, resulting in approximately 9,490 annual deaths. Most people with the disease are poor, and most do not realize they are infected. Large-scale population migrations have carried Chagas disease to new regions, which include the United States and many European countries. The disease affects more than 150 types of animals.

The disease was first described in 1909 by Brazilian physician Carlos Chagas, after whom it is named. Chagas disease is classified as a neglected tropical disease.

Signs and symptoms
Chagas disease occurs in two stages: an acute stage, which develops one to two weeks after the insect bite, and a chronic stage, which develops over many years. The acute stage is often symptom-free. When present, the symptoms are typically minor and not specific to any particular disease. Signs and symptoms include fever, malaise, headache, and enlargement of the liver, spleen, and lymph nodes. Sometimes, people develop a swollen nodule at the site of infection, which is called "Romaña's sign" if it is on the eyelid, or a "chagoma" if it is elsewhere on the skin. In rare cases (less than 1–5%), infected individuals develop severe acute disease, which can involve inflammation of the heart muscle, fluid accumulation around the heart, and inflammation of the brain and surrounding tissues, and may be life-threatening. The acute phase typically lasts four to eight weeks and resolves without treatment.

Unless treated with antiparasitic drugs, individuals remain infected with T. cruzi after recovering from the acute phase. Most chronic infections are asymptomatic, which is referred to as indeterminate chronic Chagas disease. However, over decades with the disease, approximately 30–40% of people develop organ dysfunction (determinate chronic Chagas disease), which most often affects the heart or digestive system.

The most common long-term manifestation is heart disease, which occurs in 14–45% of people with chronic Chagas disease. People with Chagas heart disease often experience heart palpitations, and sometimes fainting, due to irregular heart function. By electrocardiogram, people with Chagas heart disease most frequently have arrhythmias. As the disease progresses, the heart's ventricles become enlarged (dilated cardiomyopathy), which reduces its ability to pump blood. In many cases the first sign of Chagas heart disease is heart failure, thromboembolism, or chest pain associated with abnormalities in the microvasculature.

Also common in chronic Chagas disease is damage to the digestive system, which affects 10–21% of people. Enlargement of the esophagus or colon are the most common digestive issues. Those with enlarged esophagus often experience pain (odynophagia) or trouble swallowing (dysphagia), acid reflux, cough, and weight loss. Individuals with enlarged colon often experience constipation, and may develop severe blockage of the intestine or its blood supply. Up to 10% of chronically infected individuals develop nerve damage that can result in numbness and altered reflexes or movement. While chronic disease typically develops over decades, some individuals with Chagas disease (less than 10%) progress to heart damage directly after acute disease.

Signs and symptoms differ for people infected with T. cruzi through less common routes. People infected through ingestion of parasites tend to develop severe disease within three weeks of consumption, with symptoms including fever, vomiting, shortness of breath, cough, and pain in the chest, abdomen, and muscles. Those infected congenitally typically have few to no symptoms, but can have mild non-specific symptoms, or severe symptoms such as jaundice, respiratory distress, and heart problems. People infected through organ transplant or blood transfusion tend to have symptoms similar to those of vector-borne disease, but the symptoms may not manifest for anywhere from a week to five months. Chronically infected individuals who become immunosuppressed due to HIV infection can have particularly severe and distinct disease, most commonly characterized by inflammation in the brain and surrounding tissue or brain abscesses. Symptoms vary widely based on the size and location of brain abscesses, but typically include fever, headaches, seizures, loss of sensation, or other neurological issues that indicate particular sites of nervous system damage. Occasionally, these individuals also experience acute heart inflammation, skin lesions, and disease of the stomach, intestine, or peritoneum.

Cause
Chagas disease is caused by infection with the protozoan parasite T. cruzi, which is typically introduced into humans through the bite of triatomine bugs, also called "kissing bugs". When the insect defecates at the bite site, motile T. cruzi forms called trypomastigotes enter the bloodstream and invade various host cells. Inside a host cell, the parasite transforms into a replicative form called an amastigote, which undergoes several rounds of replication. The replicated amastigotes transform back into trypomastigotes, which burst the host cell and are released into the bloodstream. Trypomastigotes then disseminate throughout the body to various tissues, where they invade cells and replicate. Over many years, cycles of parasite replication and immune response can severely damage these tissues, particularly the heart and digestive tract.

Transmission
T. cruzi can be transmitted by various triatomine bugs in the genera Triatoma, Panstrongylus, and Rhodnius. The primary vectors for human infection are the species of triatomine bugs that inhabit human dwellings, namely Triatoma infestans, Rhodnius prolixus, Triatoma dimidiata and Panstrongylus megistus. These insects are known by a number of local names, including vinchuca in Argentina, Bolivia, Chile and Paraguay, barbeiro (the barber) in Brazil, pito in Colombia, chinche in Central America, and chipo in Venezuela. The bugs tend to feed at night, preferring moist surfaces near the eyes or mouth. A triatomine bug can become infected with T. cruzi when it feeds on an infected host. T. cruzi replicates in the insect's intestinal tract and is shed in the bug's feces. When an infected triatomine feeds, it pierces the skin and takes in a blood meal, defecating at the same time to make room for the new meal. The bite is typically painless, but causes itching. Scratching at the bite introduces the T. cruzi-laden feces into the bite wound, initiating infection.

In addition to classical vector spread, Chagas disease can be transmitted through consumption of food or drink contaminated with triatomine insects or their feces. Since heating or drying kills the parasites, drinks and especially fruit juices are the most frequent source of infection. This oral route of transmission has been implicated in several outbreaks, where it led to unusually severe symptoms, likely due to infection with a higher parasite load than from the bite of a triatomine bug— a single crushed triatomine in a food or beverage harboring T cruzi can contain about 600,000 metacyclic trypomastigotes, while triatomine fecal matter contains 3,000-4,000 per μL.

T. cruzi can be transmitted independent of the triatomine bug during blood transfusion, following organ transplantation, or across the placenta during pregnancy. Transfusion with the blood of an infected donor infects the recipient 10–25% of the time. To prevent this, blood donations are screened for T. cruzi in many countries with endemic Chagas disease, as well as the United States. Similarly, transplantation of solid organs from an infected donor can transmit T. cruzi to the recipient. This is especially true for heart transplant, which transmits T. cruzi 75–100% of the time, and less so for transplantation of the liver (0–29%) or a kidney (0–19%). An infected mother can pass T. cruzi to her child through the placenta; this occurs in up to 15% of births by infected mothers. As of 2019, 22.5% of new infections occurred through congenital transmission.

Pathophysiology
In the acute phase of the disease, signs and symptoms are caused directly by the replication of T. cruzi and the immune system's response to it. During this phase, T. cruzi can be found in various tissues throughout the body and circulating in the blood. During the initial weeks of infection, parasite replication is brought under control by production of antibodies and activation of the host's inflammatory response, particularly cells that target intracellular pathogens such as NK cells and macrophages, driven by inflammation-signaling molecules like TNF-α and IFN-γ.

During chronic Chagas disease, long-term organ damage develops over years due to continued replication of the parasite and damage from the immune system. Early in the course of the disease, T. cruzi is found frequently in the striated muscle fibers of the heart. As disease progresses, the heart becomes generally enlarged, with substantial regions of cardiac muscle fiber replaced by scar tissue and fat. Areas of active inflammation are scattered throughout the heart, with each housing inflammatory immune cells, typically macrophages and T cells. Late in the disease, parasites are rarely detected in the heart, and may be present at only very low levels.

In the heart, colon, and esophagus, chronic disease leads to a massive loss of nerve endings. In the heart, this may contribute to arrythmias and other cardiac dysfunction. In the colon and esophagus, loss of nervous system control is the major driver of organ dysfunction. Loss of nerves impairs the movement of food through the digestive tract, which can lead to blockage of the esophagus or colon and restriction of their blood supply.

Diagnosis
The presence of T. cruzi in the blood is diagnostic of Chagas disease. During the acute phase of infection, it can be detected by microscopic examination of fresh anticoagulated blood, or its buffy coat, for motile parasites; or by preparation of thin and thick blood smears stained with Giemsa, for direct visualization of parasites. Blood smear examination detects parasites in 34–85% of cases. The sensitivity increases if techniques such as microhematocrit centrifugation are used to concentrate the blood. On microscopic examination of stained blood smears, T. cruzi trypomastigotes appear as S or U-shaped organisms with a flagellum connected to the body by an undulating membrane. A nucleus and a smaller structure called a kinetoplast are visible inside the parasite's body; the kinetoplast of T. cruzi is relatively large, which helps to distinguish it from other species of trypanosomes that infect humans.

Alternatively, T. cruzi DNA can be detected by polymerase chain reaction (PCR). In acute and congenital Chagas disease, PCR is more sensitive than microscopy, and it is more reliable than antibody-based tests for the diagnosis of congenital disease because it is not affected by transfer of antibodies against T. cruzi from a mother to her baby (passive immunity). PCR is also used to monitor T. cruzi levels in organ transplant recipients and immunosuppressed people, which allows infection or reactivation to be detected at an early stage.

In chronic Chagas disease, the concentration of parasites in the blood is too low to be reliably detected by microscopy or PCR, so the diagnosis is usually made using serological tests, which detect immunoglobulin G antibodies against T. cruzi in the blood. Two positive serology results, using different test methods, are required to confirm the diagnosis. If the test results are inconclusive, additional testing methods such as Western blot can be used.

Various rapid diagnostic tests for Chagas disease are available. These tests are easily transported and can be performed by people without special training. They are useful for screening large numbers of people and testing people who cannot access healthcare facilities, but their sensitivity is relatively low, and it is recommended that a second method is used to confirm a positive result.

T. cruzi parasites can be grown from blood samples by blood culture, xenodiagnosis, or by inoculating animals with the person's blood. In the blood culture method, the person's red blood cells are separated from the plasma and added to a specialized growth medium to encourage multiplication of the parasite. It can take up to six months to obtain the result. Xenodiagnosis involves feeding the blood to triatomine insects, then examining their feces for the parasite 30 to 60 days later. These methods are not routinely used, as they are slow and have low sensitivity.

Prevention

Efforts to prevent Chagas disease have largely focused on vector control to limit exposure to triatomine bugs. Insecticide-spraying programs have been the mainstay of vector control, consisting of spraying homes and the surrounding areas with residual insecticides. This was originally done with organochlorine, organophosphate, and carbamate insecticides, which were supplanted in the 1980s with pyrethroids. These programs have drastically reduced transmission in Brazil and Chile, and eliminated major vectors from certain regions: Triatoma infestans from Brazil, Chile, Uruguay, and parts of Peru and Paraguay, as well as Rhodnius prolixus from Central America. Vector control in some regions has been hindered by the development of insecticide resistance among triatomine bugs. In response, vector control programs have implemented alternative insecticides (e.g. fenitrothion and bendiocarb in Argentina and Bolivia), treatment of domesticated animals (which are also fed on by triatomine bugs) with pesticides, pesticide-impregnated paints, and other experimental approaches. In areas with triatomine bugs, transmission of T. cruzi can be prevented by sleeping under bed nets and by housing improvements that prevent triatomine bugs from colonizing houses.

Blood transfusion was formerly the second-most common mode of transmission for Chagas disease. T. cruzi can survive in refrigerated stored blood, and can survive freezing and thawing, allowing it to persist in whole blood, packed red blood cells, granulocytes, cryoprecipitate, and platelets. The development and implementation of blood bank screening tests has dramatically reduced the risk of infection during blood transfusion. Nearly all blood donations in Latin American countries undergo Chagas screening. Widespread screening is also common in non-endemic nations with significant populations of immigrants from endemic areas, including the United Kingdom (implemented in 1999), Spain (2005), the United States (2007), France and Sweden (2009), Switzerland (2012), and Belgium (2013). Serological tests, typically ELISAs, are used to detect antibodies against T. cruzi proteins in donor blood.

Other modes of transmission have been targeted by Chagas disease prevention programs. Treating T. cruzi-infected mothers during pregnancy reduces the risk of congenital transmission of the infection. To this end, many countries in Latin America have implemented routine screening of pregnant women and infants for T. cruzi infection, and the World Health Organization recommends screening all children born to infected mothers to prevent congenital infection from developing into chronic disease. Similarly to blood transfusions, many countries with endemic Chagas disease screen organs for transplantation with serological tests.

There is no vaccine against Chagas disease. Several experimental vaccines have been tested in animals infected with T. cruzi and were able to reduce parasite numbers in the blood and heart, but no vaccine candidates had undergone clinical trials in humans as of 2016.

Management
Chagas disease is managed using antiparasitic drugs to eliminate T. cruzi from the body, and symptomatic treatment to address the effects of the infection. As of 2018, benznidazole and nifurtimox were the antiparasitic drugs of choice for treating Chagas disease, though benznidazole is the only drug available in most of Latin America. For either drug, treatment typically consists of two to three oral doses per day for 60 to 90 days. Antiparasitic treatment is most effective early in the course of infection: it eliminates T. cruzi from 50 to 80% of people in the acute phase (WHO: "nearly 100 %" ), but only 20–60% of those in the chronic phase. Treatment of chronic disease is more effective in children than in adults, and the cure rate for congenital disease approaches 100% if treated in the first year of life. Antiparasitic treatment can also slow the progression of the disease and reduce the possibility of congenital transmission. Elimination of T. cruzi does not cure the cardiac and gastrointestinal damage caused by chronic Chagas disease, so these conditions must be treated separately. Antiparasitic treatment is not recommended for people who have already developed dilated cardiomyopathy.

Benznidazole is usually considered the first-line treatment because it has milder adverse effects than nifurtimox, and its efficacy is better understood. Both benznidazole and nifurtimox have common side effects that can result in treatment being discontinued. The most common side effects of benznidazole are skin rash, digestive problems, decreased appetite, weakness, headache, and sleeping problems. These side effects can sometimes be treated with antihistamines or corticosteroids, and are generally reversed when treatment is stopped. However, benznidazole is discontinued in up to 29% of cases. Nifurtimox has more frequent side effects, affecting up to 97.5% of individuals taking the drug. The most common side effects are loss of appetite, weight loss, nausea and vomiting, and various neurological disorders including mood changes, insomnia, paresthesia and peripheral neuropathy. Treatment is discontinued in up to 75% of cases. Both drugs are contraindicated for use in pregnant women and people with liver or kidney failure. As of 2019, resistance to these drugs has been reported.

Complications
In the chronic stage, treatment involves managing the clinical manifestations of the disease. The treatment of Chagas cardiomyopathy is similar to that of other forms of heart disease. Beta blockers and ACE inhibitors may be prescribed, but some people with Chagas disease may not be able to take the standard dose of these drugs because they have low blood pressure or a low heart rate. To manage irregular heartbeats, people may be prescribed anti-arrhythmic drugs such as amiodarone, or have a pacemaker implanted. Blood thinners may be used to prevent thromboembolism and stroke. Chronic heart disease caused by untreated T. cruzi infection is a common reason for heart transplantation surgery. Because transplant recipients take immunosuppressive drugs to prevent organ rejection, they are monitored using PCR to detect reactivation of the disease. People with Chagas disease who undergo heart transplantation have higher survival rates than the average heart transplant recipient.

Mild gastrointestinal disease may be treated symptomatically, such as by using laxatives for constipation, or taking a prokinetic drug like metoclopramide before meals to relieve esophageal symptoms. Surgery to sever the muscles of the lower esophageal sphincter (cardiomyotomy) may be performed in more severe cases of esophageal disease, and surgical removal of the affected part of the organ may be required for advanced megacolon and megaesophagus.

Epidemiology

In 2019, an estimated 6.5 million people worldwide had Chagas disease, with approximately 173,000 new infections and 9,490 deaths each year. The disease resulted in a global annual economic burden estimated at US$7.2 billion in 2013, 86% of which is borne by endemic countries. Chagas disease results in the loss of over 800,000 disability-adjusted life years each year.

The endemic area of Chagas disease stretches from the southern United States to northern Chile and Argentina, with Bolivia (6.1%), Argentina (3.6%), and Paraguay (2.1%) exhibiting the highest prevalence of the disease. Within continental Latin America, Chagas disease is endemic to 21 countries: Argentina, Belize, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, French Guiana, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay, and Venezuela. In endemic areas, due largely to vector control efforts and screening of blood donations, annual infections and deaths have fallen by 67% and more than 73% respectively from their peaks in the 1980s to 2010. Transmission by insect vector and blood transfusion has been completely interrupted in Uruguay (1997), Chile (1999), and Brazil (2006), and in Argentina, vectorial transmission had been interrupted in 13 of the 19 endemic provinces as of 2001. During Venezuela's humanitarian crisis, vectorial transmission has begun occurring in areas where it had previously been interrupted, and Chagas disease seroprevalence rates have increased. Transmission rates have also risen in the Gran Chaco region due to insecticide resistance and in the Amazon basin due to oral transmission.

While the rate of vector-transmitted Chagas disease has declined throughout most of Latin America, the rate of orally transmitted disease has risen, possibly due to increasing urbanization and deforestation bringing people into closer contact with triatomines and altering the distribution of triatomine species. Orally transmitted Chagas disease is of particular concern in Venezuela, where 16 outbreaks have been recorded between 2007 and 2018.

Chagas exists in two different ecological zones. In the Southern Cone region, the main vector lives in and around human homes. In Central America and Mexico, the main vector species lives both inside dwellings and in uninhabited areas. In both zones, Chagas occurs almost exclusively in rural areas, where T. cruzi also circulates in wild and domestic animals. T. cruzi commonly infects more than 100 species of mammals across Latin America including opossums (Didelphis spp.), armadillos, marmosets, bats, various rodents and dogs all of which can be infected by the vectors or orally by eating triatomine bugs and other infected animals. For entomophagous animals this is a common mode. Didelphis spp. are unique in that they do not require the triatomine for transmission, completing the life cycle through their own urine and feces. Veterinary transmission also occurs through vertical transmission through the placenta, blood transfusion and organ transplants.

Non-endemic countries
Though Chagas is traditionally considered a disease of rural Latin America, international migration has dispersed those with the disease to numerous non-endemic countries, primarily in North America and Europe. As of 2020, approximately 300,000 infected people are living in the United States, and in 2018 it was estimated that 30,000 to 40,000 people in the United States had Chagas cardiomyopathy. The vast majority of cases in the United States occur in immigrants from Latin America, but local transmission is possible. Eleven triatomine species are native to the United States, and some southern states have persistent cycles of disease transmission between insect vectors and animal reservoirs, which include woodrats, possums, raccoons, armadillos and skunks. However, locally acquired infection is very rare: only 28 cases were documented from 1955 to 2015. As of 2013, the cost of treatment in the United States was estimated to be US$900 million annually (global cost $7 billion), which included hospitalization and medical devices such as pacemakers.

Chagas disease affected approximately 68,000 to 123,000 people in Europe as of 2019. Spain, which has a high rate of immigration from Latin America, has the highest prevalence of the disease. It is estimated that 50,000 to 70,000 people in Spain are living with Chagas disease, accounting for the majority of European cases. The prevalence varies widely within European countries due to differing immigration patterns. Italy has the second highest prevalence, followed by the Netherlands, the United Kingdom, and Germany.

History

T. cruzi likely circulated in South American mammals long before the arrival of humans on the continent. T. cruzi has been detected in ancient human remains across South America, from a 9000-year-old Chinchorro mummy in the Atacama Desert, to remains of various ages in Minas Gerais, to an 1100-year-old mummy as far north as the Chihuahuan Desert near the Rio Grande. Many early written accounts describe symptoms consistent with Chagas disease, with early descriptions of the disease sometimes attributed to Miguel Diaz Pimenta (1707), Luís Gomes Ferreira (1735), and Theodoro J. H. Langgaard (1842).

The formal description of Chagas disease was made by Carlos Chagas in 1909 after examining a two-year-old girl with fever, swollen lymph nodes, and an enlarged spleen and liver. Upon examination of her blood, Chagas saw trypanosomes identical to those he had recently identified from the hindgut of triatomine bugs and named Trypanosoma cruzi in honor of his mentor, Brazilian physician Oswaldo Cruz. He sent infected triatomine bugs to Cruz in Rio de Janeiro, who showed the bite of the infected triatomine could transmit T. cruzi to marmoset monkeys as well. In just two years, 1908 and 1909, Chagas published descriptions of the disease, the organism that caused it, and the insect vector required for infection. Almost immediately thereafter, at the suggestion of Miguel Couto, then professor of the Faculdade de Medicina do Rio de Janeiro, the disease was widely referred to as "Chagas disease". Chagas' discovery brought him national and international renown, but in highlighting the inadequacies of the Brazilian government's response to the disease, Chagas attracted criticism to himself and to the disease that bore his name, stifling research on his discovery and likely frustrating his nomination for the Nobel Prize in 1921.

In the 1930s, Salvador Mazza rekindled Chagas disease research, describing over a thousand cases in Argentina's Chaco Province. In Argentina, the disease is known as mal de Chagas-Mazza in his honor. Serological tests for Chagas disease were introduced in the 1940s, demonstrating that infection with T. cruzi was widespread across Latin America. This, combined with successes eliminating the malaria vector through insecticide use, spurred the creation of public health campaigns focused on treating houses with insecticides to eradicate triatomine bugs. The 1950s saw the discovery that treating blood with crystal violet could eradicate the parasite, leading to its widespread use in transfusion screening programs in Latin America. Large-scale control programs began to take form in the 1960s, first in São Paulo, then various locations in Argentina, then national-level programs across Latin America. These programs received a major boost in the 1980s with the introduction of pyrethroid insecticides, which did not leave stains or odors after application and were longer-lasting and more cost-effective. Regional bodies dedicated to controlling Chagas disease arose through support of the Pan American Health Organization, with the Initiative of the Southern Cone for the Elimination of Chagas Diseases launching in 1991, followed by the Initiative of the Andean countries (1997), Initiative of the Central American countries (1997), and the Initiative of the Amazon countries (2004).

Treatments
Fexinidazole, an antiparasitic drug approved for treating African trypanosomiasis, has shown activity against Chagas disease in animal models. As of 2019, it is undergoing phase II clinical trials for chronic Chagas disease in Spain. Other drug candidates include GNF6702, a proteasome inhibitor that is effective against Chagas disease in mice and is undergoing preliminary toxicity studies, and AN4169, which has had promising results in animal models.

A number of experimental vaccines have been tested in animals. In addition to subunit vaccines, some approaches have involved vaccination with attenuated T. cruzi parasites or organisms that express some of the same antigens as T. cruzi but do not cause human disease, such as Trypanosoma rangeli or Phytomonas serpens. DNA vaccination has also been explored. As of 2019, vaccine research has mainly been limited to small animal models.

Diagnostic tests
As of 2018, standard diagnostic tests for Chagas disease were limited in their ability to measure the effectiveness of antiparasitic treatment, as serological tests may remain positive for years after T. cruzi is eliminated from the body, and PCR may give false-negative results when the parasite concentration in the blood is low. Several potential biomarkers of treatment response are under investigation, such as immunoassays against specific T. cruzi antigens, flow cytometry testing to detect antibodies against different life stages of T. cruzi, and markers of physiological changes caused by the parasite, such as alterations in coagulation and lipid metabolism.

Another research area is the use of biomarkers to predict the progression of chronic disease. Serum levels of tumor necrosis factor alpha, brain and atrial natriuretic peptide, and angiotensin-converting enzyme 2 have been studied as indicators of the prognosis of Chagas cardiomyopathy.

T. cruzi shed acute-phase antigen (SAPA), which can be detected in blood using ELISA or Western blot, has been used as an indicator of early acute and congenital infection. An assay for T. cruzi antigens in urine has been developed to diagnose congenital disease.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Chagas disease


text:
Christiaan Barnard

Christiaan Neethling Barnard (8 November 1922 – 2 September 2001) was a South African cardiac surgeon who performed the world's first human-to-human heart transplant operation. On 3 December 1967, Barnard transplanted the heart of accident victim Denise Darvall into the chest of 54-year-old Louis Washkansky who regained full consciousness and was able to talk easily with his wife, before dying eighteen days later of pneumonia, largely brought on by the anti-rejection drugs that suppressed his immune system. Barnard had told Mr. and Mrs. Washkansky that the operation had an 80% chance of success, an assessment which has been criticised as misleading. Barnard's second transplant patient, Philip Blaiberg, whose operation was performed at the beginning of 1968, returned home from the hospital and lived for a year and a half.

Born in Beaufort West, Cape Province, Barnard studied medicine and practised for several years in his native South Africa. As a young doctor experimenting on dogs, Barnard developed a remedy for the infant defect of intestinal atresia. His technique saved the lives of ten babies in Cape Town and was adopted by surgeons in Britain and the United States. In 1955, he travelled to the United States and was initially assigned further gastrointestinal work by Owen Harding Wangensteen at the University of Minnesota. He was introduced to the heart-lung machine, and Barnard was allowed to transfer to the service run by open heart surgery pioneer Walt Lillehei. Upon returning to South Africa in 1958, Barnard was appointed head of the Department of Experimental Surgery at the Groote Schuur Hospital, Cape Town.

He retired as head of the Department of Cardiothoracic Surgery in Cape Town in 1983 after rheumatoid arthritis in his hands ended his surgical career. He became interested in anti-aging research, and in 1986 his reputation suffered when he promoted Glycel, an expensive "anti-aging" skin cream, whose approval was withdrawn by the United States Food and Drug Administration soon thereafter. During his remaining years, he established the Christiaan Barnard Foundation, dedicated to helping underprivileged children throughout the world. He died in 2001 at the age of 78 after an asthma attack.

Early life
Barnard grew up in Beaufort West, Cape Province, Union of South Africa. His father, Adam Barnard, was a minister in the Dutch Reformed Church. One of his four brothers, Abraham, was a "blue baby" who died of a heart problem at the age of three (Barnard would later guess that it was tetralogy of Fallot). The family also experienced the loss of a daughter who was stillborn and who had been the fraternal twin of Barnard's older brother Johannes, who was twelve years older than Christiaan. Barnard matriculated from the Beaufort West High School in 1940, and went to study medicine at the University of Cape Town Medical School, where he obtained his MB ChB in 1945.

His father served as a missionary to mixed-race people. His mother, the former Maria Elisabeth de Swart, instilled in the surviving brothers the belief that they could do anything they set their minds to.

Career
Barnard did his internship and residency at the Groote Schuur Hospital in Cape Town, after which he worked as a general practitioner in Ceres, a rural town in the Cape Province. In 1951, he returned to Cape Town where he worked at the City Hospital as a Senior Resident Medical Officer, and in the Department of Medicine at Groote Schuur as a registrar. He completed his master's degree, receiving Master of Medicine in 1953 from the University of Cape Town. In the same year he obtained a doctorate in medicine (MD) from the same university for a dissertation titled "The treatment of tuberculous meningitis".

Soon after qualifying as a doctor, Barnard performed experiments on dogs while investigating intestinal atresia, congenital, life-threatening obstructions in the intestines. He followed a medical hunch that this was caused by inadequate blood flow to the fetus. After nine months and forty-three attempts, Barnard was able to reproduce this condition in a fetus puppy by tying off some of the blood supply to a puppy's intestines and then placing the animal back in the womb, after which it was born some two weeks later, with the condition of intestinal atresia. He was also able to cure the condition by removing the piece of intestine with inadequate blood supply. The mistake of previous surgeons had been attempting to reconnect ends of intestine which themselves still had inadequate blood supply. To be successful, it was typically necessary to remove between 15 and 20 centimeters of intestine (6 to 8 inches). Jannie Louw used this innovation in a clinical setting, and Barnard's method saved the lives of ten babies in Cape Town. This technique was also adapted by surgeons in Britain and the US. In addition, Barnard analyzed 259 cases of tubercular meningitis.

Owen Wangensteen at the University of Minnesota in the United States had been impressed by the work of Alan Thal, a young South African doctor working in Minnesota. Wangensteen asked the Groote Schuur Head of Medicine John Brock if he might recommend any similarly talented South Africans, and Brock recommended Barnard. In December 1955, Barnard travelled to Minneapolis, Minnesota to begin a two-year scholarship under Chief of Surgery Wangensteen, who assigned Barnard more work on the intestines, which Barnard accepted even though he wanted to move onto something new. Simply by luck, whenever Barnard needed a break from this work, he could wander across the hall and talk with Vince Gott who ran the lab for open-heart surgery pioneer Walt Lillehei. Gott had begun to develop a technique of running blood backwards through the veins of the heart so Lillehei could more easily operate on the aortic valve (McRae writes, "It was the type of inspired thinking that entranced Barnard"). In March 1956, Gott asked Barnard to help him run the heart-lung machine for an operation. Shortly thereafter, Wangensteen agreed to let Barnard switch to Lillehei's service. It was during this time that Barnard became acquainted with fellow future heart transplantation surgeon Norman Shumway. Barnard also became friendly with Gil Campbell, who had demonstrated that a dog's lung could be used to oxygenate blood during open-heart surgery. (The year before Barnard arrived, Lillehei and Campbell had used this procedure for twenty minutes during surgery on a 13-year-old boy with ventricular septal defect, and the boy had made a full recovery.) Barnard and Campbell met regularly for early breakfast. In 1958, Barnard received a Master of Science in Surgery for a thesis titled "The aortic valve – problems in the fabrication and testing of a prosthetic valve". The same year he was awarded a Ph.D. for his dissertation titled "The aetiology of congenital intestinal atresia". Barnard described the two years he spent in the United States as "the most fascinating time in my life."

Upon returning to South Africa in 1958, Barnard was appointed head of the Department of Experimental Surgery at Groote Schuur hospital, as well as holding a joint post at the University of Cape Town. He was promoted to full-time lecturer and Director of Surgical Research at the University of Cape Town. In 1960, he flew to Moscow in order to meet Vladimir Demikhov, a top expert on organ transplants (later he credited Demikhov's accomplishment saying that "if there is a father of heart and lung transplantation then Demikhov certainly deserves this title.") In 1961 he was appointed Head of the Division of Cardiothoracic Surgery at the teaching hospitals of the University of Cape Town. He rose to associate professor in the Department of Surgery at the University of Cape Town in 1962. Barnard's younger brother Marius, who also studied medicine, eventually became Barnard's right-hand man at the department of Cardiac Surgery. Over time, Barnard became known as a brilliant surgeon with many contributions to the treatment of cardiac diseases, such as the Tetralogy of Fallot and Ebstein's anomaly. He was promoted to Professor of Surgical Science in the Department of Surgery at the University of Cape Town in 1972. In 1981, Barnard became a founding member of the World Cultural Council. Among the recognition he received over the years, he was named Professor Emeritus in 1984.

Historical context
Following the first successful kidney transplant in 1953, in the United States, Barnard performed the second kidney transplant in South Africa in October 1967, the first having been done in Johannesburg the previous year.

On 23 January 1964, James Hardy at the University of Mississippi Medical Center in Jackson, Mississippi, performed the world's first heart transplant and world's first cardiac xenotransplant by transplanting the heart of a chimpanzee into a desperately ill and dying man. This heart did beat in the patient's chest for approximately 60 to 90 minutes. The patient, Boyd Rush, died without regaining consciousness.

Barnard had experimentally transplanted forty-eight hearts into dogs, which was about a fifth the number that Adrian Kantrowitz had performed at Maimonides Medical Center in New York and about a sixth the number Norman Shumway had performed at Stanford University in California. Barnard had no dogs which had survived longer than ten days, unlike Kantrowitz and Shumway who had had dogs survive for more than a year.

With the availability of new breakthroughs introduced by several pioneers, also including Richard Lower at the Medical College of Virginia, several surgical teams were in a position to prepare for a human heart transplant. Barnard had a patient willing to undergo the procedure, but as with other surgeons, he needed a suitable donor.

During the Apartheid era in South Africa, non-white persons and citizens were not given equal opportunities in the medical professions. At Groote Schuur Hospital, Hamilton Naki was an informally taught surgeon. He started out as a gardener and cleaner. One day he was asked to help out with an experiment on a giraffe. From this modest beginning, Naki became principal lab technician and taught hundreds of surgeons, and assisted with Barnard's organ transplant program. Barnard said, "Hamilton Naki had better technical skills than I did. He was a better craftsman than me, especially when it came to stitching, and had very good hands in the theatre". A popular myth, propagated principally by a widely discredited documentary film called Hidden Heart   and an erroneous newspaper article, maintains incorrectly that Naki was present during the Washkansky transplant.

First human-to-human heart transplant
Barnard performed the world's first human-to-human heart transplant operation in the early morning hours of Sunday 3 December 1967. Louis Washkansky, a 54-year-old grocer who was suffering from diabetes and incurable heart disease, was the patient. Barnard was assisted by his brother Marius Barnard, as well as a team of thirty staff members. The operation lasted approximately five hours.

Barnard stated to Washkansky and his wife Ann Washkansky that the transplant had an 80% chance of success. This has been criticised by the ethicists Peter Singer and Helga Kuhse as making claims for chances of success to the patient and family which were "unfounded" and "misleading". Barnard later wrote, "For a dying man it is not a difficult decision because he knows he is at the end. If a lion chases you to the bank of a river filled with crocodiles, you will leap into the water, convinced you have a chance to swim to the other side." The donor heart came from a young woman, Denise Darvall, who had been rendered brain dead in an accident on 2 December 1967, while crossing a street in Cape Town. On examination at Groote Schuur hospital, Darvall had two serious fractures in her skull, with no electrical activity in her brain detected, and no sign of pain when ice water was poured into her ear. Coert Venter and Bertie Bosman requested permission from Darvall's father for Denise's heart to be used in the transplant attempt. The afternoon before his first transplant, Barnard dozed at his home while listening to music. When he awoke, he decided to modify Shumway and Lower's technique. Instead of cutting straight across the back of the atrial chambers of the donor heart, he would avoid damage to the septum and instead cut two small holes for the venae cavae and pulmonary veins. Prior to the transplant, rather than wait for Darvall's heart to stop beating, at his brother Marius Barnard's urging, Christiaan had injected potassium into her heart to paralyse it and render her technically dead by the whole-body standard. Twenty years later, Marius Barnard recounted, "Chris stood there for a few moments, watching, then stood back and said, 'It works.'"

Washkansky survived the operation and lived for 18 days; he died from pneumonia, possibly due to the immunosuppressive drugs he was taking.

Additional heart transplants
Barnard and his patient received worldwide publicity. As a 2017 BBC retrospective article describes, "Journalists and film crews flooded into Cape Town's Groote Schuur Hospital, soon making Barnard and Washkansky household names." Barnard himself was described as "charismatic" and "photogenic." And the operation was initially reported as "successful" even though Washkansky only lived a further 18 days.

Worldwide, approximately 100 transplants were performed by various doctors during 1968. However, only a third of these patients lived longer than three months. Many medical centers stopped performing transplants. In fact, a US National Institutes of Health publication states, "Within several years, only Shumway's team at Stanford was attempting transplants."

Barnard's second transplant operation was conducted on 2 January 1968, and the patient, Philip Blaiberg, survived for 19 months. Blaiberg's heart was donated by Clive Haupt, a 24-year-old black man who suffered a stroke, inciting controversy (especially in the African-American press) during the time of South African apartheid. Dirk van Zyl, who received a new heart in 1971, was the longest-lived recipient, surviving over 23 years.

Between December 1967 and November 1974 at Groote Schuur Hospital in Cape Town, South Africa, ten heart transplants were performed, as well as a heart and lung transplant in 1971. Of these ten patients, four lived longer than 18 months, with two of these four becoming long-term survivors. One patient, Dorothy Fischer, lived for over thirteen years and another for over twenty-four years.

Full recovery of donor heart function often takes place over hours or days, during which time considerable damage can occur. Other deaths to patients can occur from preexisting conditions. For example, in pulmonary hypertension the patient's right ventricle has often adapted to the higher pressure over time and, although diseased and hypertrophied, is often capable of maintaining circulation to the lungs. Barnard designed the idea of the heterotopic (or "piggy back" transplant) in which the patient's diseased heart is left in place while the donor heart is added, essentially forming a "double heart". Barnard performed the first such heterotopic heart transplant in 1974.

From November 1974 through December 1983, 49 consecutive heterotopic heart transplants on 43 patients were performed at Groote Schuur. The survival rate for patients at one year was over 60%, as compared to less than 40% with standard transplants, and the survival rate at five years was over 36% as compared to less than 20% with standard transplants.

Many surgeons gave up cardiac transplantation due to poor results, often due to rejection of the transplanted heart by the patient's immune system. Barnard persisted until the advent of cyclosporine, an effective immunosuppressive drug, which helped revive the operation throughout the world. He also attempted xenotransplantation in two human patients, utilizing a baboon heart and chimpanzee heart, respectively.

Public life
Barnard was an outspoken opponent of South Africa's laws of apartheid, and was not afraid to criticise his nation's government, although he had to temper his remarks to some extent to travel abroad. Rather than leaving his homeland, he used his fame to campaign for a change in the law. Christiaan's brother, Marius Barnard, went into politics, and was elected to the legislature from the Progressive Federal Party. Barnard later stated that the reason he never won the Nobel Prize in Physiology or Medicine was probably because he was a "white South African".

Shortly before his visit to Kenya in 1978, the following was written about his views regarding race relations in South Africa; "While he believes in the participation of Africans in the political process of South Africa, he is opposed to a one-man-one-vote system in South Africa".

In answering a hypothetical question on how he would solve the race problem were he a "benevolent dictator in South Africa", Barnard stated the following in a long interview at the Weekly Review:
 * While "I would abolish Social discrimination", political discrimination would continue.
 * He favoured the total division of the country along racial lines. His words were; "I somehow feel ... but we may have to divide South Africa into two equal divisions". In a follow-up question about where the coloured people would end up in that scenario, he replied that 'I would include them in the white South Africa".
 * That coloured people have "always been accepted" among whites.
 * That "the black man will not accept this view" of universal suffrage.
 * That "we are still out of the Olympic games" despite the fact that "in the field of sports where we have virtually integrated completely."
 * Regarding the Soweto uprising, he claimed "there was ... a lot of external stirring up of turbulence". Regarding the anger from the black population when Steve Biko was murdered, he said that "I think that something like $50,000 came in from outside to work up feelings at that funeral."
 * He stated that the National Party members were as upset about Biko's murder as were blacks; "The white community was thoroughly upset, let me tell you. The nationalists themselves were very upset."

The interview ended with the following summary from he himself; "I often say that, like King Lear, South Africa is a country more sinned against than sinning."

Personal life
Barnard's first marriage was to Aletta Gertruida Louw, a nurse, whom he married in 1948 while practising medicine in Ceres. The couple had two children: Deirdre (born 1950) and Andre (1951–1984). International fame took a toll on his family, and in 1969, Barnard and his wife divorced. In 1970, he married heiress Barbara Zoellner when she was 19, the same age as his son, and they had two children: Frederick (born 1972) and Christiaan Jr. (born 1974). He divorced Zoellner in 1982. Barnard married for a third time in 1988 to Karin Setzkorn, a young model. They also had two children, Armin (born 1989) and Lara (born 1997). This last marriage also ended in divorce in 2000.

Barnard described in his autobiography The Second Life a one-night extramarital affair with Italian film star Gina Lollobrigida, that occurred in January 1968. During that visit to Rome he received an audience from Pope Paul VI.

In October 2016, US Congresswoman Ann McLane Kuster stated that Barnard sexually assaulted her when she was 23 years old. According to Kuster, Barnard attempted to grope her under her skirt while she was seated at a business luncheon with US Representative Pete McCloskey, for whom she worked at the time.

Retirement
Barnard retired as Head of the Department of Cardiothoracic Surgery in Cape Town in 1983 after developing rheumatoid arthritis in his hands which ended his surgical career. He had struggled with arthritis since 1956, when it was diagnosed during his postgraduate work in the United States. After retirement, he spent two years as the Scientist-In-Residence at the Oklahoma Transplantation Institute in the United States and as an acting consultant for various institutions.

He had by this time become very interested in anti-aging research, and his reputation suffered in 1986 when he promoted Glycel, an expensive "anti-aging" skin cream, whose approval was withdrawn by the United States Food and Drug Administration soon thereafter. He also spent time as a research advisor to the Clinique la Prairie, in Switzerland, where the controversial "rejuvenation therapy" was practised.

Barnard divided the remainder of his years between Austria, where he established the Christiaan Barnard Foundation, dedicated to helping underprivileged children throughout the world, and his game farm in Beaufort West, South Africa. In his later years, he had Basal-cell carcinoma (skin cancer) on his face, for which he was treated in Parow, South Africa.

Death
Christiaan Barnard died on 2 September 2001, while on holiday in Paphos, Cyprus. Early reports stated that he had died of a heart attack, but an autopsy showed his death was caused by a severe asthma attack.

Books
Barnard wrote two autobiographies. His first book, One Life, was published in 1969 (ISBN 0245599525) and sold copies worldwide. Some of the proceeds were used to set up the Chris Barnard Fund for research into heart disease and heart transplants in Cape Town. His second autobiography, The Second Life, was published in 1993, eight years before his death (ISBN 0947461388).

Apart from his autobiographies, Barnard wrote books including:
 * The Donor
 * Your Healthy Heart
 * In the Night Season
 * The Best Medicine
 * Arthritis Handbook: How to Live With Arthritis
 * Good Life Good Death: A Doctor's Case for Euthanasia and Suicide
 * South Africa: Sharp Dissection
 * 50 Ways to a Healthy Heart
 * Body Machine

title: Christiaan Barnard