Environmental impact of war

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Environmental_impact_of_war 

 

Kuwaiti oil fires set by retreating Iraqi forces during the Gulf War caused a dramatic decrease in air quality.

Agent Orange, a herbicide, being sprayed on farmland during the Vietnam War

Study of the environmental impact of war focuses on the modernization of warfare and its increasing effects on the environment. Scorched earth methods have been used for much of recorded history. However, the methods of modern warfare cause far greater devastation on the environment. The progression of warfare from chemical weapons to nuclear weapons has increasingly created stress on ecosystems and the environment. Specific examples of the environmental impact of war include World War I, World War II, the Vietnam War, the Rwandan Civil War, the Kosovo War and the Gulf War.

Historical events

Vietnam

Defoliant spray run, part of Operation Ranch Hand, during the Vietnam War by UC-123B Provider aircraft

The Vietnam War had significant environmental implications due to chemical agents which were used to destroy militarily-significant vegetation. Enemies found an advantage in remaining invisible by blending into a civilian population or taking cover in dense vegetation and opposing armies which targeted natural ecosystems. The US military used “more than 20 million gallons of herbicides [...] to defoliate forests, clear growth along the borders of military sites and eliminate enemy crops." The chemical agents gave the US an advantage in wartime efforts. However, the vegetation was unable to regenerate and it left behind bare mudflats which still existed years after spraying. Not only was the vegetation affected, but also the wildlife: "a mid-1980s study by Vietnamese ecologists documented just 24 species of birds and 5 species of mammals present in sprayed forests and converted areas, compared to 145–170 bird species and 30–55 kinds of mammals in intact forest." The uncertain long-term effects of these herbicides are now being discovered by looking at modified species distribution patterns through habitat degradation and loss in wetland systems, which absorbed the runoff from the mainland.

Africa

Throughout Africa, war has been a major factor in the decline of wildlife populations inside national parks and other protected areas. However, a growing number of ecological restoration initiatives, including in Rwanda's Akagera National Park and Mozambique's Gorongosa National Park, have shown that wildlife populations and whole ecosystems can be successfully rehabilitated even after devastating conflicts. Experts have emphasized that solving social, economic, and political problems is essential for the success of such efforts.

Rwanda

The Rwandan genocide led to the killing of roughly 800,000 Tutsis and moderate Hutus. The war created a massive migration of nearly 2 million Hutus fleeing Rwanda over the course of just a few weeks to refugee camps in Tanzania and now modern day the Democratic Republic of the Congo. This large displacement of people in refugee camps puts pressure on the surrounding ecosystem. Forests were cleared in order to provide wood for building shelters and creating cooking fires: “these people suffered from harsh conditions and constituted an important threat impact to natural resources.” Consequences from the conflict also included the degradation of National Parks and Reserves. Another big problem was the population crash in Rwanda shifted personnel and capital to other parts of the country, thereby making it hard to protect wildlife.

World War II

World War II (WWII) drove a vast increase in production, militarized the production and transportation of commodities, and introduced many new environmental consequences, which can still be seen today. World War II was wide-ranging in its destruction of humans, animals, and materials. The postwar effects of World War II, both ecological and social, are still visible decades after the conflict ended.

During World War II, new technology was used to create aircraft, which were used to conduct air raids. During the war, aircraft were used to transport resources both to and from different military bases and drop bombs on enemy, neutral, and friendly targets alike. These activities damaged habitats.

Similar to wildlife, ecosystems also suffer from noise pollution which is produced by military aircraft. During World War II, aircraft acted as a vector for the transportation of exotics whereby weeds and cultivated species were brought to oceanic island ecosystems by way of aircraft landing strips which were used as refueling and staging stations during operations in the Pacific theater. Before the war, the isolated islands around Europe were inhabited by a high number of endemic species. During World War II, aerial warfare had an enormous influence on fluctuating population dynamics.

In August 1945, after fighting World War II for almost four years, the United States of America dropped an atomic bomb over the city of Hiroshima in Japan. About 70,000 people died in the first nine seconds after the bombing of Hiroshima, which was comparable to the death toll which resulted from the devastating Operation Meetinghouse air raid over Tokyo. Three days after the bombing of Hiroshima, the United States dropped a second atomic bomb on the industrial city of Nagasaki, instantly killing 35,000 people. The nuclear weapons released catastrophic loads of energy. Once the bombs were blasted, the temperatures reached about 7200 °F. With temperatures that high, all the flora and fauna were destroyed along with the infrastructure and human lives in the impact zones. When the atomic bombs were dropped, they released enormous quantities of energy and radioactive particles. The radioactive particles which were released contaminated the land and water for miles around. The initial blasts increased the surface temperatures, along with the crushing winds which were caused by the initial blasts, the trees and buildings which were in their paths were all destroyed.

European forests experienced traumatic impacts which resulted from fighting during the war. Behind the combat zones, timber from cut down trees was removed in order to clear up the paths for fighting. The shattered forests in the battle zones faced exploitation.

The use of heavily hazardous chemicals was first initiated during World War II. The long-term effects of chemicals result from both their potential persistence and the poor disposal program of nations with stockpiled weapons. During World War I (WW I), German chemists developed chlorine gas and mustard gas. The development of these gases led to many casualties, and lands were poisoned both on and near the battlefields.

Later in World War II, chemists developed even more harmful chemical bombs, which were packaged in barrels and directly deposited in the oceans. The disposal of the chemicals in ocean runs the risk of metal-based containers corroding and leaching the chemical contents of the vessel into the ocean. Through the chemical disposal in the ocean, the contaminates may be spread throughout the various components of the ecosystems damaging marine and terrestrial ecosystems.

Marine ecosystems during World War II were damaged not only from chemical contaminates, but also from wreckage from naval ships, which leaked oil into the water. Oil contamination in the Atlantic Ocean due to World War II shipwrecks is estimated at over 15 million tonnes. Oil spills are difficult to clean up and take many years to clean. To this day, traces of oil can still be found in the Atlantic Ocean from the naval shipwrecks which happened during World War II.

The use of chemicals during war helped increase the scale of chemical industries and it also helped to show the government the value of scientific research to the government. The development of chemical research during the war also lead to the postwar development of agricultural pesticides. The creation of pesticides was an upside for the years after the war.

The environmental impacts of World War II were very drastic, which allowed them to be seen in the Cold War and be seen today. The impacts of conflict, chemical contaminations, and aerial warfare all contribute to reduction in the population of global flora and fauna, as well as a reduction in species diversity.

In 1946, in the U.S. Zone of Germany, the United States military advised the government to prepare accommodations and employment for the people who were bombed out of their cities. The answer was a special garden program that would provide new land for the people to live in. This included land to provide food needed for the people as well. Forests were then surveyed for good soil that was suitable for crop production.This meant that the forest would be cut down in order to make land for farms and housing.The forestry program would be used to exploit the forests of Germany for future resources and control the war potential of Germany. In this program about 23,500,000 fest meters of lumber were produced out of the forests.

Aluminum was one of the biggest resources affected by Would War II. Bauxite, an aluminum ore and the mineral cryolite were essential, as well as requiring massive amounts of electrical power.

Gulf War and Iraq War

During the 1991 Gulf War, the Kuwaiti oil fires were a result of the scorched earth policy of Iraqi forces retreating from Kuwait. The Gulf War oil spill, regarded as the worst oil spill in history, was caused when Iraqi forces opened valves at the Sea Island oil terminal and dumped oil from several tankers into the Persian Gulf. Oil was also dumped in the middle of the desert.

Just before the 2003 Iraq War, Iraq also set fire to various oil fields.

Some American military personnel complained of Gulf War syndrome, typified by symptoms including immune system disorders and birth defects in their children. Whether it is due to time spent in active service during the war or for other reasons remains controversial.

Other examples

• 1938 Yellow River flood, created by the Nationalist government in Central China during the early stages of the Second Sino-Japanese War in an attempt to halt the rapid advance of the Japanese forces. It has been called the "largest act of environmental warfare in history".
• Beaufort's Dyke, used as a dumping ground for bombs
• Jiyeh Power Station oil spill, bombed by the Israeli Air Force during the 2006 Israel-Lebanon conflict.
• Formerly Used Defense Sites, a U.S. military program which is responsible for environmental restoration
• K5 Plan, an attempt by the government of the People's Republic of Kampuchea to seal off Khmer Rouge guerrilla infiltration routes into Cambodia between 1985 and 1989, resulting in environmental degradation.
• Saudi Arabian-led intervention in Yemen, an intervention in a civil war in the Middle East, disrupted the water-energy-food security nexus in an already resource-poor country. The war and the conflict led to the contamination of water and agricultural lands.

Environmental hazards

Resources are a key source of conflict between nations: "after the end of the Cold War in particular, many have suggested that environmental degradation will exacerbate scarcities and become an additional source of armed conflict." A nation's survival depends on resources from the environment. Resources that are a source of armed conflict include territory, strategic raw materials, sources of energy, water, and food. In order to maintain resource stability, chemical and nuclear warfare have been used by nations in order to protect or extract resources, and during conflict. These agents of war have been used frequently: “about 125,000 tons of chemical agent were employed during World War I, and about 96,000 tons during the Viet-Nam conflict.” Nerve gas, also known as organophosphorous anticholinesterases, was used at lethal levels against human beings and destroyed a high number of nonhuman vertebrate and invertebrate populations. However, contaminated vegetation would mostly be spared, and would only pose a threat to herbivores. The result of innovations in chemical warfare led to a broad range of different chemicals for war and domestic use, but also resulted in unforeseen environmental damage.

The progression of warfare and its effects on the environment continued with the invention of weapons of mass destruction. While today, weapons of mass destruction act as deterrents and the use of weapons of mass destruction during World War II created significant environmental destruction. On top of the great loss in human life, “natural resources are usually the first to suffer: forests and wild life animals are wiped out.” Nuclear warfare imposes both direct and indirect effects on the environment. The physical destruction due to the blast or by the biospheric damage due to ionizing radiation or radiotoxicity directly affect ecosystems within the blast radius. Also, the atmospheric or geospheric disturbances caused by the weapons can lead to weather and climate changes.

Unexploded ordnance

Military campaigns require large quantities of explosive weapons, a fraction of which will not detonate properly and leave unexploded weapons. This creates a serious physical and chemical hazard for the civilian populations living in areas which were once war zones, due to the possibility of detonation after the conflict, as well as the leaching of chemicals into the soil and groundwater.

Agent Orange

Agent Orange was one of the herbicides and defoliants used by the British military during the Malayan Emergency and the U.S. military in its herbicidal warfare program, Operation Ranch Hand, during the Vietnam War. An estimated 21,136,000 gal. (80 000 m³) of Agent Orange were sprayed across South Vietnam, exposing 4.8 million Vietnamese people to Agent Orange, and resulting in 400,000 deaths and disabilities, and 500,000 children born with birth defects. Many Commonwealth personnel who handled and/or used Agent Orange during and decades after the 1948–1960 Malayan conflict suffered from serious exposure of dioxin. Agent Orange also caused major soil erosion to areas in Malaya. An estimated 10,000 civilians and possibly insurgents in Malaya also suffered heavily from defoliant effects, though many historians likely agreed it was more than 10,000 given that Agent Orange was used on a large scale in the Malayan conflict and unlike the U.S., the British government manipulated the numbers and kept its secret very tight in fear of negative world public opinion.

Testing of nuclear armaments

Testing of nuclear armaments has been carried out at various places including Bikini Atoll, the Marshall Islands Pacific Proving Grounds, New Mexico in the US, Mururoa Atoll, Maralinga in Australia, and Novaya Zemlya in the former Soviet Union, among others.

Downwinders are individuals and communities who are exposed to radioactive contamination and/or nuclear fallout from atmospheric and/or underground nuclear weapons testing, and nuclear accidents.

Strontium-90

The United States government studied the post-war effects of Strontium-90, a radioactive isotope which is found in nuclear fallout . The Atomic Energy Commission discovered that “Sr-90, which is chemically similar to calcium, can accumulate in bones and possibly lead to cancer”. Sr-90 found its way into humans through the ecological food chain as fallout in the soil, was picked up by plants, further concentrated in herbivorous animals, and eventually consumed by humans.

Depleted uranium munitions

The use of depleted uranium in munitions is controversial because of numerous questions about potential long-term health effects. Normal functioning of the kidney, brain, liver, heart, and numerous other systems can be affected by uranium exposure, because in addition to being weakly radioactive, uranium is a toxic metal. It remains weakly radioactive because of its long half-life. The aerosol produced during impact and combustion of depleted uranium munitions can potentially contaminate wide areas around the impact sites or can be inhaled by civilians and military personnel. In a three-week period of conflict in Iraq during 2003, it was estimated over 1000 tons of depleted uranium munitions were used mostly in cities. The U.S. Department of Defense claims that no human cancer of any type has been seen as a result of exposure to either natural or depleted uranium.

Yet, U.S. DoD studies using cultured cells and laboratory rodents continue to suggest the possibility of leukemogenic, genetic, reproductive, and neurological effects from chronic exposure.

In addition, the UK Pensions Appeal Tribunal Service in early 2004 attributed birth defect claims from a February 1991 Gulf War combat veteran to depleted uranium poisoning. Campaign Against Depleted Uranium (Spring, 2004) Also, a 2005 epidemiology review concluded: "In aggregate the human epidemiological evidence is consistent with increased risk of birth defects in offspring of persons exposed to DU."

Fossil fuel use

With the high degree of mechanization of the military large amounts of fossil fuels are used. Fossil fuels are a major contributor to global warming and climate change, issues of increasing concern. Access to oil resources is also a factor for instigating a war.

The United States Department of Defense (DoD) is a government body with the highest use of fossil fuel in the world. According to the 2005 CIA World Factbook, when compared with the consumption per country the DoD would rank 34th in the world in average daily oil use, coming in just behind Iraq and just ahead of Sweden.

Waste incineration

At U.S. bases during the 21st-century wars in Iraq and Afghanistan, human waste was burned in open pits along with munitions, plastic, electronics, paint, and other chemicals. The carcinogenic smoke is suspected to have injured some soldiers exposed to it.

Intentional flooding

Flooding can be used as scorched earth policy through using water to render land unusable. It can also be used to prevent the movement of enemy combatants. During the Second Sino-Japanese War, dykes on the Yellow and the Yangtze Rivers were breached to halt the advance of Japanese forces. During the Siege of Leiden in 1573, the dykes were breached to halt the advance of Spanish forces. During Operation Chastise during the Second World War, the Eder and Sorpe river dams in Germany were bombed by the Royal Air Force, flooding a large area and halting industrial manufacture used by the Germans in the war effort.

Militarism and the environment

Human security has traditionally been solely linked to military activities and defense. Scholars and institutions like the International Peace Bureau are now increasingly calling for a more holistic approach to security, particularly including an emphasis on the interconnections and interdependencies that exist between humans and the environment. Military activity has significant impacts on the environment. Not only can war be destructive to the socioenvironment, but military activities produce extensive amounts of greenhouse gases (that contribute to anthropogenic climate change), pollution, and cause resource depletion, among other environmental impacts.

Greenhouse gas emissions and pollution

Several studies have found a strong positive correlation between military spending and increased greenhouse gas emissions, with the impact of military spending on carbon emissions being more pronounced for countries of the Global North (i.e.: OECD developed countries). Accordingly, the US military is estimated to be the number one fossil fuel consumer in the world.

Additionally, military activities involve high emissions of pollution. The Pentagon's director of environment, safety and occupational health, Maureen Sullivan, has stated that they work with approximately 39,000 contaminated sites. Indeed, the US military is also considered one of the largest generators of pollution in the world. Combined, the top five US chemical companies only produce one fifth of the toxins produced by the Pentagon. In Canada, the Department of National Defence readily admits it is the largest energy consumer of the Government of Canada, and a consumer of “high volumes of hazardous materials”.

Military pollution is a worldwide occurrence. Armed forces from around the world were responsible for the emission of two thirds of chlorofluorocarbons (CFCs) that were banned in the 1987 Montreal Protocol for causing damage to the ozone layer. In addition, naval accidents during the Cold War have dropped at minimum 50 nuclear warheads and 11 nuclear reactors into the ocean, they remain on the ocean floor.

Land and resource use

Military land use needs (such as for bases, training, storage etc.) often displace people from their lands and homes. Military activity uses solvents, fuels and other toxic chemicals which can leach toxins into the environment that remain there for decades and even centuries. Furthermore, heavy military vehicles can cause damage to soil and infrastructure. Military-caused noise pollution can also diminish the quality of life for nearby communities as well as their ability to rear or hunt animals to support themselves. Advocates raise concerns of environmental racism and/or environmental injustice as it is largely marginalized communities that are displaced and/or affected.

Militaries are also highly resource intensive. Weapons and military equipment make up the second largest international trade sector. The International Peace Bureau says that more than fifty percent of the helicopters in the world are for military use, and approximately twenty-five percent of jet fuel consumption is by military vehicles. These vehicles are also extremely inefficient, carbon intensive, and discharge emissions that are more toxic than those of other vehicles.

Activist responses

Military funding is, at present, higher than ever before, and activists are concerned about the implication for greenhouse gas emissions and climate change. They advocate for demilitarization, citing the high greenhouse gas emissions and support the redirection of those funds to climate action. Currently the world spends about 2.2% of global GDP on military funding according to the World Bank. It is estimated that it would cost approximately one percent of global GDP yearly until 2030 to reverse the climate crisis. Moreover, activists emphasize the need for prevention and the avoidance of costly clean up. Currently, the expense for cleaning up military contaminated site is at least $500 billion. Finally, activists point to social issues such as extreme poverty and advocate for more funding to be redirected from military expenses to these causes.

Groups working for demilitarization and peace include the International Peace Bureau, Canadian Voice of Women for Peace, The Rideau Institute, Ceasefire.ca, Project Ploughshares, and Codepink. See List of anti-war organizations for more groups.

Militaries' positive effects on the environment

There are examples from around the world of nations’ armed forces aiding in land management and conservation. For example, in Bhuj, India, military forces stationed there helped to reforest the area; in Pakistan, the Army took part in the Billion tree tsunami, working with civilians to reforest land in KPK and Punjab.; in Venezuela, it is part of the National Guard’s responsibilities to protect natural resources. Additionally, military endorsement of environmentally friendly technology such as renewable energy may have the potential to generate public support for these technologies. Finally, certain military technologies like GPS and drones are helping environmental scientists, conservationists, ecologists and restoration ecologists conduct better research, monitoring, and remediation.

War and environmental law

From a legal standpoint, environmental protection during times of war and military activities is addressed partially by international environmental law. Further sources are also found in areas of law such as general international law, the laws of war, human rights law and local laws of each affected country. Several United Nations treaties, including the Fourth Geneva Convention, the 1972 World Heritage Convention and the 1977 Environmental Modification Convention have provisions to limit the environmental impacts of war.

The Environmental Modification Convention is an international treaty prohibiting the military or other hostile use of environmental modification techniques having widespread, long-lasting or severe effects. The Convention bans weather warfare, which is the use of weather modification techniques for the purposes of inducing damage or destruction. This treaty is in force and has been ratified (accepted as binding) by leading military powers.

Thiomersal and vaccines

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Thiomersal_and_vaccines 

Thiomersal (or thimerosal) is a mercury compound which is used as a preservative in some vaccines. Anti-vaccination activists promoting the incorrect claim that vaccination causes autism have asserted that the mercury in thiomersal is the cause There is no scientific evidence to support this claim. The idea that thiomersal in vaccines might have detrimental effects originated with anti-vaccination activists and was sustained by them and especially through the action of plaintiffs' lawyers.

The potential impact of thiomersal on autism has been investigated extensively. Multiple lines of scientific evidence have shown that thiomersal does not cause autism. For example, the clinical symptoms of mercury poisoning differ significantly from those of autism. In addition, multiple population studies have found no association between thiomersal and autism, and rates of autism have continued to increase despite removal of thiomersal from vaccines. Thus, major scientific and medical bodies such as the Institute of Medicine and World Health Organization (WHO) as well as governmental agencies such as the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) reject any role for thiomersal in autism or other neurodevelopmental disorders. In spite of the consensus of the scientific community, some parents and advocacy groups continue to contend that thiomersal is linked to autism and the claim is still stated as if it were fact in anti-vaccination propaganda, notably that of Robert F. Kennedy Jr., through his group Children's Health Defense. Thiomersal is no longer used in most children's vaccines in the United States, with the exception of some types of flu shots. While exposure to mercury may result in damage to brain, kidneys, and developing fetus, the scientific consensus is that thiomersal has no such effects.

This controversy has caused harm due to parents attempting to treat their autistic children with unproven and possibly dangerous treatments, discouraging parents from vaccinating their children due to fears about thiomersal toxicity and diverting resources away from research into more promising areas for the cause of autism. Thousands of lawsuits have been filed in the U.S. to seek damages from alleged toxicity from vaccines, including those purportedly caused by thiomersal. US courts have ruled against multiple representative test cases involving thiomersal. A 2011 journal article described the vaccine-autism connection as "perhaps, the most damaging medical hoax of the last 100 years".

History

Thiomersal (also spelled thimerosal, especially in the United States) is an organomercury compound used as a preservative in vaccines to prevent bacterial and fungal contamination. Following a mandated review of mercury-containing food and drugs in 1999, the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics (AAP) determined that under the existing vaccination schedule "some children could be exposed to a cumulative level of mercury over the first 6 months of life that exceeds one of the federal guidelines on methyl mercury." They asked vaccine makers to remove thiomersal from vaccines as quickly as possible as a precautionary measure, and it was rapidly phased out of most US and EU vaccines, but is still used in multi-dose vials of flu vaccines in the U.S. No vaccines in the European Union currently contain thiomersal as a preservative. In the context of perceived increased autism rates and increased number of vaccines in the childhood vaccination schedule, some parents believed the action to remove thiomersal was an indication that the preservative caused autism.

It was introduced as a preservative in the 1930s to prevent the growth of infectious organisms such as bacteria and fungi, and has been in use in vaccines and other products such as immunoglobulin preparations and ophthalmic and nasal solutions. Vaccine manufacturers have used preservatives to prevent microbial growth during the manufacturing process or when packaged as "multi-dose" products to allow for multiple punctures of the same vial to dispense multiple vaccinations with less fear of contamination. After the FDA Modernization Act of 1997 mandated a review and risk assessment of all mercury-containing food and drugs, vaccine manufacturers responded to FDA requests made in December 1998 and April 1999 to provide detailed information about the thiomersal content of their preparations.

A review of the data showed that while the vaccine schedule for infants did not exceed FDA, Agency for Toxic Substances and Disease Registry (ATSDR), or WHO guidelines on mercury exposure, it could have exceeded Environmental Protection Agency (EPA) standards for the first six months of life, depending on the vaccine formulation and the weight of the infant. The review also highlighted difficulty interpreting toxicity of the ethylmercury in thiomersal because guidelines for mercury toxicity were based primarily on studies of methylmercury, a different mercury compound with different toxicologic properties. Multiple meetings were scheduled among various government officials and scientists from multiple agencies to discuss the appropriate response to this evidence. There was a wide range of opinions on the urgency and significance of the safety of thiomersal, with some toxicologists suggesting there was no clear evidence that thiomersal was harmful and other participants like Neal Halsey, director of the Institute of Vaccine Safety at Johns Hopkins School of Public Health, strongly advocating removal of thiomersal from vaccines due to possible safety risks. In the process of forming the response to this information, the participants attempted to strike a balance between acknowledging possible harm from thiomersal and the risks involved if childhood vaccinations were delayed or stopped.

Upon conclusion of their review, the FDA, in conjunction with the other members of the US Public Health Service (USPHS), the National Institutes of Health (NIH), CDC and Health Resources and Services Administration (HRSA), in a joint statement with the AAP in July 1999 concluded that there was "no evidence of harm caused by doses of thimerosal found in vaccines, except for local hypersensitivity reactions."

Despite the lack of convincing evidence of toxicity of thiomersal when used as a vaccine preservative, the USPHS and AAP determined that thiomersal should be removed from vaccines as a purely precautionary measure. This action was based on the precautionary principle, which assumes that there is no harm in exercising caution even if it later turns out to be unnecessary. The CDC and AAP reasoned that despite the lack of evidence of significant harm in the use of thiomersal in vaccines, the removal of this preservative would increase the public confidence in the safety of vaccines. Although thiomersal was largely removed from routine infant vaccines by summer 2001 in the U.S., some vaccines continue to contain non-trace amounts of thiomersal, mainly in multi-dose vaccines targeted against influenza, meningococcal disease and tetanus.

In 2004 Quackwatch posted an article saying that chelation therapy has been falsely promoted as effective against autism, and that practitioners falsified diagnoses of metal poisoning to "trick" parents into having their children undergo the process. As of 2008, between 2–8% of children with autism had undergone the therapy.

Rationale for concern

Reports of autism cases per 1,000 children grew dramatically in the U.S. from 1996 to 2007. It is unknown how much, if any, growth came from changes in autism's prevalence.

Although intended to increase public confidence in vaccinations, the decision to remove thiomersal instead led to some parents suspecting thiomersal as a cause of autism. This concern over a vaccine-autism link grew from a confluence of several underlying factors. First, methylmercury had for decades been the subject of widespread environmental and media concern after two highly publicized episodes of poisonings in the 1950s and 1960s in Minamata Bay, Japan from industrial waste and in the 1970s in Iraq from fungicide contamination of wheat. These incidents led to new research on methylmercury safety and culminated in the publication of an array of confusing recommendations by public health agencies in the 1990s warning against methylmercury exposure in adults and pregnant women, which ensured a continued high public awareness of mercury toxicity. Second, the vaccine schedule for infants expanded in the 1990s to include more vaccines, some of which, including the Hib vaccine, DTaP vaccine and hepatitis B vaccine, could have contained thiomersal. Third, the number of diagnoses of autism grew in the 1990s, leading parents of these children to search for an explanation for the apparent rise in diagnoses, including considering possible environmental factors. The dramatic increase in reported cases of autism during the 1990s and early 2000s is largely attributable to changes in diagnostic practices, referral patterns, availability of services, age at diagnosis, and public awareness, and it is unknown whether autism's true prevalence increased during the period. Nevertheless, some parents believed that there was a growing "autism epidemic" and connected these three factors to conclude that the increase in number of vaccines, and specifically the mercury in thiomersal in those vaccines, was causing a dramatic increase in the incidence of autism.

Advocates of a thiomersal-autism link also relied on indirect evidence from the scientific literature, including analogy with neurotoxic effects of other mercury compounds, the reported epidemiologic association between autism and vaccine use, and extrapolation from in vitro experiments and animal studies. Studies conducted by Mark Geier and his son David Geier have been the most frequently cited research by parents advocating a link between thiomersal and autism. This research by Geier has received considerable criticism for methodological problems in his research, including not presenting methods and statistical analyses to others for verification, improperly analyzing data taken from Vaccine Adverse Event Reporting System, as well as either mislabelling or confusing fundamental statistical terms in his papers, leading to results that were "uninterpretable".

Publicity of concern

Several months after the recommendation to have thiomersal removed from vaccines was published, a speculative article was published in Medical Hypotheses, a non-peer-reviewed journal, by parents who launched the parental advocacy group SafeMinds to promote the theory that thiomersal caused autism. The controversy began to gain legitimacy in the eyes of the public and gained widening support within certain elements in the autism advocacy community as well as in the political arena, with U.S. Representative Dan Burton openly supporting this movement and holding a number of Congressional hearings on the subject.

Further support for the association between autism and thiomersal appeared in an article by Robert F. Kennedy Jr. in the magazines Rolling Stone and Salon.com alleging a government conspiracy at a CDC meeting to conceal the dangers of thiomersal to protect the pharmaceutical industry, and a book written by David Kirby, Evidence of Harm, dramatizing the lives of parents of autistic children, with both authors participating in media interviews to promote their work and the controversy. Although the allegations by Kennedy were denied and a US Senate committee investigation later found no evidence to substantiate the most serious allegations, the story had already been well publicized by leveraging Kennedy's celebrity. Salon magazine subsequently amended Kennedy's article five times due to factual errors and later retracted it completely on 16 January 2011, stating that the works of critics of the article and evidence of the flaws in the science connecting autism and vaccines undermined the value of the article to the editors.

Meanwhile, during this time of increased media publicity of the controversy, public health officials and institutions did little to rebut the concerns and speculative theories being offered. Media attention and polarization of the debate has also been fueled by personal injury lawyers who took out full-page ads in prominent newspapers and offered financial support for expert witnesses who dissented from the scientific consensus that there is no convincing evidence for a link between thiomersal and autism. Paul Offit, a leading vaccine researcher and advocate, has said that the media has a tendency to provide false balance by perpetually presenting both sides of an issue even when only one side is supported by the evidence and thereby giving a platform for the spread of misinformation.

Despite the consensus from experts that there is no link between thiomersal and autism, many parents continue to believe that such a link exists. These parents share the viewpoint that autism is not just treatable, but curable through "biomedical" interventions and have been frustrated by the lack of progress from more "mainline" scientists in finding this cure. Instead, they have supported an alternative community of like-minded parents, physicians and scientists who promote this belief. This mindset has taught these parents to challenge the expertise from the mainstream scientific community. Parents have also been influenced by an extensive network of anti-vaccination organizations such as Robert F. Kennedy Jr.'s Children's Health Defense and a large number of online anti-vaccination websites that present themselves as an alternative source for evidence using pseudoscientific claims. These websites use emotional appeals to gather support and frame the controversy as an adversarial dispute between parents and a conspiracy of doctors and scientists. Advocates for a thiomersal-autism link have also relied on celebrities like model Jenny McCarthy and information presented on Don Imus' Imus in the Morning radio show to persuade the public to their cause, instead of relying only on "dry" scientific papers and scientists. McCarthy has published a book describing her personal experience with her autistic son and appeared on The Oprah Winfrey Show to promote the hypothesis of vaccines causing autism. Bitterness over this issue has led to numerous threats made against the CDC as well as researchers like Offit, with increased security placed by the CDC in response to these threats.

Scientific evaluation

Rationale for doubting link

Various lines of evidence undermine a proposed link between thiomersal and autism. For example, although advocates of a thiomersal-autism link consider autism a form of "mercury poisoning," the typical symptoms of mercury toxicity are significantly different from symptoms seen in autism. Likewise, the neuroanatomic and histopathologic features of the brains of patients who have mercury poisoning, both with methylmercury as well as ethylmercury, have significant differences from the brains of people with autism. Previous episodes of widespread mercury toxicity in a population such as in Minamata Bay, Japan would also be expected to lead to documentation of a significant rise in autism or autism-like behavior in children should autism be caused by mercury poisoning. However, research on several episodes of acute and chronic mercury poisoning have not documented any such rise in autism-like behavior. Although some parents cite an association between the timing of onset of autistic symptoms with the timing of vaccinations as evidence of an environmental cause such as thiomersal, this line of reasoning can be misleading. Associations such as these do not establish causation as the two occurring together may be only coincidental in nature. Also, genetic disorders that have no environmental triggers such as Rett syndrome and Huntington's disease nevertheless have specific ages when they begin to show symptoms, suggesting specific ages of onset of symptoms does not necessarily require an environmental cause.

Although the concern for a thiomersal-autism link was originally derived from indirect evidence based on the known potent neurotoxic effects of methylmercury, recent studies show these feared effects were likely overestimated. Ethylmercury, such as in thiomersal, clears much faster from the body after administration than methylmercury, suggesting total mercury exposure over time is much less with ethylmercury. Currently used methods of estimating brain deposition of mercury likely overestimates the amounts deposited due to ethylmercury, and ethylmercury also decomposes quicker in the brain than methylmercury, suggesting a lower risk of brain damage. These findings show that the assumptions that originally led to concern about the toxicity of ethylmercury, which were based on direct comparison to methylmercury, were flawed.

Population studies

Multiple studies have been performed on data from large populations of children to study the relationship between the use of vaccines containing thiomersal, and autism and other neurodevelopmental disorders. Almost all of these studies have found no association between thiomersal-containing vaccines (TCVs) and autism, and studies done after the removal of thiomersal from vaccines have nevertheless shown autism rates continuing to increase. The only epidemiologic research that has found a purported link between TCVs and autism has been conducted by Mark Geier, whose flawed research has not been given any weight by independent reviews.

In Europe, a cohort study of 467,450 Danish children found no association between TCVs and autism or autism spectrum disorders (ASDs), nor any dose-response relationship between thiomersal and ASDs that would be suggestive of toxic exposure. An ecological analysis that studied 956 Danish children diagnosed with autism likewise did not show an association between autism and thiomersal. A retrospective cohort study on 109,863 children in the United Kingdom found no association between TCVs and autism, but a possible increased risk for tics. Analysis in this study also showed a possible protective effect with respect to general developmental disorders, attention-deficit disorder, and otherwise unspecified developmental delay. Another UK study based on a prospective cohort of 13,617 children likewise found more associated benefits than risks from thiomersal exposure with respect to developmental disorders. Because the Danish and UK studies involved only diphtheria-tetanus-pertussis (DTP) or diphtheria-tetanus (DT) vaccines, they are less relevant for the higher thiomersal exposure levels that occurred in the U.S.

In North America, a Canadian study of 27,749 children in Quebec showed that thiomersal was unrelated to the increasing trend in pervasive developmental disorders (PDDs). In fact, the study noted that rates of PDDs were higher in the birth cohorts with no thiomersal when compared to those with medium or high levels of exposure. A study performed in the US which analyzed data from 78,829 children enrolled in HMOs taken from the Vaccine Safety Datalink (VSD) did not show any consistent association between TCVs and neurodevelopmental outcomes, noting different results from data in different HMOs. A study performed in California found that removal of thiomersal from vaccines did not decrease the rates of autism, suggesting that thiomersal could not be the primary cause of autism. A study on children from Denmark, Sweden and California likewise argued against TCVs being causally associated with autism.

Scientific consensus

In 2001 the Centers for Disease Control and Prevention and the National Institutes of Health asked the U.S. National Academy of Science's (NAS) Institute of Medicine to establish an independent expert committee to review hypotheses about existing and emerging immunization safety concerns. This initial report found that based on indirect and incomplete evidence available at the time, there was inadequate evidence to accept or reject a thiomersal-autism link, though it was biologically plausible.

Since this report was released, several independent reviews have examined the body of published research for a possible thiomersal-autism link by examining the theoretical mechanisms of thiomersal causing harm and by reviewing the in vitro, animal, and population studies that have been published. These reviews determined that no evidence exists to establish thiomersal as the cause of autism or other neurodevelopmental disorders.

The scientific consensus on the subject is reflected in a follow up report that was subsequently published in 2004 by the Institute of Medicine, which took into account new data that had been published since the 2001 report. The committee noted, in response to those who cite in vitro or animal models as evidence for the link between autism and thiomersal:

However, the experiments showing effects of thimerosal on biochemical pathways in cell culture systems and showing abnormalities in the immune system or metal metabolism in people with autism are provocative; the autism research community should consider the appropriate composition of the autism research portfolio with some of these new findings in mind. However, these experiments do not provide evidence of a relationship between vaccines or thimerosal and autism. In the absence of experimental or human evidence that vaccination (either the MMR vaccine or the preservative thimerosal) affects metabolic, developmental, immune, or other physiological or molecular mechanisms that are causally related to the development of autism, the committee concludes that the hypotheses generated to date are theoretical only.he committee concludes:

Thus, based on this body of evidence, the committee concludes that the evidence favors rejection of a causal relationship between thimerosal-containing vaccines and autism. [bold in original]

Further evidence of the scientific consensus includes the rejection of a causal link between thiomersal and autism by multiple national and international scientific and medical bodies including the American Medical Association, the American Academy of Pediatrics, the American College of Medical Toxicology, the Canadian Paediatric Society, the U.S. National Academy of Sciences, the Food and Drug Administration, Centers for Disease Control and Prevention, the World Health Organization, the Public Health Agency of Canada, and the European Medicines Agency.

A 2011 journal article reflects this point of view and described the vaccine-autism connection as "the most damaging medical hoax of the last 100 years".

Consequences

The suggestion that thiomersal has contributed to autism and other neurodevelopmental disorders has had a number of effects. Public health officials believe fear driven by advocates of a thiomersal-autism link has caused parents to avoid vaccination or adopt "made up" vaccination schedules that expose their children to increased risk from preventable diseases such as measles and pertussis. Advocates of a thiomersal-autism link have also helped enact laws in six states (California, Delaware, Illinois, Missouri, New York and Washington) between 2004 and 2006 to limit the use of thiomersal given to pregnant women and children, although later attempts in 2009 in twelve other states failed to pass. These laws can be temporarily suspended, but vaccine advocates doubt their utility given the lack of evidence for danger with thiomersal in vaccines. Vaccine advocates are also concerned that passage of such laws help fuel a backlash against vaccination and contribute to doubts about the safety of vaccines that are unwarranted.

During the period of time of removal of thiomersal, the CDC and AAP asked doctors to delay the birth dose of hepatitis B vaccine in children not at risk for hepatitis. This decision, though following the precautionary principle, nevertheless sparked confusion, controversy and some harm. Approximately 10% of hospitals suspended the use of hepatitis B vaccine for all newborns, and one child born to a Michigan mother infected with hepatitis B virus died of it. Similarly, a study found that the number of hospitals who failed to properly vaccinate infants of hepatitis B seropositive mothers rose by over 6 times. This is a potential negative outcome given the high probability that infants who acquire hepatitis B infection at birth will develop the infection in a chronic form and possibly liver cancer.

The notion that thiomersal causes autism has led some parents to have their children treated with costly and potentially dangerous therapies such as chelation therapy, which is typically used to treat heavy metal poisoning, due to parental fears that autism is a form of "mercury poisoning". As many as 2 to 8% of autistic children in the U.S., numbering as many as several thousand children per year, receive mercury-chelating agents. Although critics of using chelation therapy as an autism treatment point to a lack of any evidence to support its use, hundreds of doctors prescribe these medications despite possible side effects including nutritional deficiencies as well as damage to the liver and kidney. The popularity of this therapy caused a "public health imperative" that led the U.S. National Institute of Mental Health (NIMH) to commission a study about chelation in autism by studying DMSA, a chelating agent used for lead poisoning, despite worries from critics that there would be no chance it would show positive results and it would be unlikely to convince parents to not use the therapy. Ultimately, the study was halted due to ethical concerns that there would be too much risk to children with autism who did not have toxic levels of mercury or lead due to a new animal study showing possible cognitive and emotional problems associated with DMSA. A 5-year-old autistic boy died from cardiac arrest immediately after receiving chelation therapy treatment using EDTA in 2005.

The notion has also diverted attention and resources away from efforts to determine the causes of autism. The 2004 Institute of Medicine report committee recommended that while it supported "targeted research that focuses on better understanding the disease of autism, from a public health perspective the committee does not consider a significant investment in studies of the theoretical vaccine-autism connection to be useful at this time." Alison Singer, a senior executive of Autism Speaks, resigned from the group in 2009 in a dispute over whether to fund more research on links between vaccination and autism, saying, "There isn't an unlimited pot of money, and every dollar spent looking where we know the answer isn't is one less dollar we have to spend where we might find new answers."

Court cases

From 1988 until August 2010, 5,632 claims relating to autism were made to Office of Special Masters of the U.S. Court of Federal Claims (commonly known as the "Vaccine Court") which oversees vaccine injury claims, of which one case has received compensation, 738 cases have been dismissed with no compensations made, and with the remaining cases pending. In the one case which received compensation, the U.S. government agreed to pay for injury to a child that had a pre-existing mitochondrial disorder who developed autism-like symptoms after multiple vaccinations, some of which included thiomersal. Citing the inability to rule out a role of these vaccinations in exacerbating her underlying mitochondrial disorder as the rationale for payment, CDC officials cautioned against generalizing this one case to all autism-related vaccine cases as most patients with autism do not have a mitochondrial disorder. In February 2009, this court also ruled on three autism-related cases, each exploring different mechanisms that plaintiffs proposed linked thiomersal-containing vaccines with autism. Three judges independently found no evidence that vaccines caused autism and denied the plaintiffs compensation. Since these same mechanisms formed the basis for the vast majority of remaining autism-related vaccine injury cases, the chance for compensation in any of these cases has significantly decreased. In March 2010, the court ruled in three other test cases that thiomersal-containing vaccines do not cause autism.

 

Beta thalassemia

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Beta_thalassemia 

 

Beta-thalassemia
Other names	Microcytemia, beta type
Beta thalassemia genetics, the picture shows one example of how beta thalassemia is inherited. The beta globin gene is located on chromosome 11. A child inherits two beta globin genes (one from each parent).
Specialty	Hematology
Types	Thalassemia minor, intermediate and major
Causes	Mutations in the HBB gene
Diagnostic method	DNA analysis
Treatment	Depends on type (see types)

Beta thalassemias (β thalassemias) are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Global annual incidence is estimated at one in 100,000. Beta thalassemias occur due to malfunctions in the hemoglobin subunit beta or HBB. The severity of the disease depends on the nature of the mutation.

HBB blockage over time leads to decreased beta-chain synthesis. The body's inability to construct new beta-chains leads to the underproduction of HbA (adult hemoglobin). Reductions in HbA available overall to fill the red blood cells in turn leads to microcytic anemia. Microcytic anemia ultimately develops in respect to inadequate HBB protein for sufficient red blood cell functioning. Due to this factor, the patient may require blood transfusions to make up for the blockage in the beta-chains. Repeated blood transfusions cause severe problems associated with iron overload.

Signs and symptoms

The hand of a person with severe anemia (left, wearing ring) compared to one without

Three main forms have been described: thalassemia minor, thalassemia intermedia, and thalassemia major which vary from asymptomatic or mild symptoms to severe anemia requiring lifelong transfusions. Individuals with beta thalassemia major (those who are homozygous for thalassemia mutations, or inheriting 2 mutations) usually present within the first two years of life with symptomatic severe anemia, poor growth, and skeletal abnormalities. Untreated thalassemia major eventually leads to death, usually by heart failure; therefore, prenatal screening is very important. Those with beta thalassemia intermedia (those who are compound heterozygoutes for the beta thalassemia mutation) usually present later in life with mild to moderate symptoms of anemia. Beta thalassemia trait (also known as beta thalassemia minor) involves heterozygous inheritance of a beta-thalassemia mutation and patients usually have borderline microcytic, hypochromic anemia and they are usually asymptomatic or have mild symptoms. Beta thalassemia minor can also present as beta thalassemia silent carriers; those who inherit a beta thalassemic mutation but have no hematologic abnormalities nor symptoms. Some people with thalassemia are susceptible to health complications that involve the spleen (hypersplenism) and gallstones (due to hyperbilirubinemia from peripheral hemolysis). These complications are mostly found in thalassemia major and intermedia patients.

Excess iron (from hemolysis or transfusions) causes serious complications within the liver, heart, and endocrine glands. Severe symptoms include liver cirrhosis, liver fibrosis, and in extreme cases, liver cancer. Heart failure, growth impairment, diabetes and osteoporosis are life-threatening conditions which can be caused by beta thalassemia major. The main cardiac abnormalities seen as a result of beta thalassemia and iron overload include left ventricular systolic and diastolic dysfunction, pulmonary hypertension, valvulopathy, arrhythmias, and pericarditis. Increased gastrointestinal iron absorption is seen in all grades of beta thalassemia, and increased red blood cell destruction by the spleen due to ineffective erythropoiesis further releases additional iron into the bloodstream.

Additional symptoms of beta thalassemia major or intermedia include the classic symptoms of moderate to severe anemia including fatigue, growth and developmental delay in childhood, leg ulcers and organ failure. Ineffective erythropoiesis (red blood cell production) can also lead to compensatory bone marrow expansion which can then lead to bony changes/deformities, bone pain and craniofacial abnormalities. Extramedullary organs such as the liver and spleen that can also undergo erythropoiesis become activated leading to hepatosplenomegaly (enlargement of the liver and spleen). Other tissues in the body can also become sites of erythropoiesis, leading to extramedullary hematopoietic psuedotumors which may cause compressive symptoms if they occur in the thoracic cavity or spinal canal.

Cause

Mutations

Two major groups of mutations can be distinguished:

• Nondeletion forms: These defects, in general, involve a single base substitution or small insertions near or upstream of the β globin gene. Most often, mutations occur in the promoter regions preceding the beta-globin genes. Less often, abnormal splice variants are believed to contribute to the disease.
• Deletion forms: Deletions of different sizes involving the β globin gene produce different syndromes such as (β^o) or hereditary persistence of fetal hemoglobin syndromes.

Mutations are characterized as (βo) if they prevent any formation of β globin chains, mutations are characterized as (β+) if they allow some β globin chain formation to occur.

Name	Older synonyms	Description	Alleles
Thalassemia minor		Heterozygous form: Only one of β globin alleles bears a mutation. Individuals will suffer from microcytic anemia. Detection usually involves lower than normal mean corpuscular volume value (<80 fL).	β+/β βo/β
Thalassemia intermedia		Affected individuals can often manage a normal life but may need occasional transfusions, e.g., at times of illness or pregnancy, depending on the severity of their anemia.	β+/β+ βo/β+
Thalassemia major	Mediterranean anemia; Cooley anemia	Homozygous form: Occurs when both alleles have thalassemia mutations. This is a severe microcytic, hypochromic anemia. Untreated, it causes anemia, splenomegaly and severe bone deformities, and progresses to death before age 20. Treatment consists of periodic blood transfusion; splenectomy for splenomegaly and chelation of transfusion-related iron overload.	βo/βo

mRNA assembly

Protein HBB PDB 1a00: this is a healthy Beta Globin Protein

Beta thalassemia is a hereditary disease affecting hemoglobin. As with about half of all hereditary diseases, an inherited mutation damages the assembly of the messenger-type RNA (mRNA) that is transcribed from a chromosome. DNA contains both the instructions (genes) for stringing amino acids together into proteins, as well as stretches of DNA that play important roles in regulating produced protein levels.

In thalassemia, an additional, contiguous length or a discontinuous fragment of non-coding instructions is included in the mRNA. This happens because the mutation obliterates the boundary between the intronic and exonic portions of the DNA template. Because all the coding sections may still be present, normal hemoglobin may be produced and the added genetic material, if it produces pathology, instead disrupts regulatory functions enough to produce anemia. Hemoblogin's normal alpha and beta subunits each have an iron-containing central portion (heme) that allows the protein chain of a subunit to fold around it. Normal adult hemoglobin contains 2 alpha and 2 beta subunits. Thalassemias typically affect only the mRNAs for production of the beta chains (hence the name). Since the mutation may be a change in only a single base (single-nucleotide polymorphism), on-going efforts seek gene therapies to make that single correction.

Risk factors

Family history and ancestry are factors that increase the risk of beta thalassemia. Depending on family history, if a person's parents or grandparents had beta thalassemia major or intermedia, there is a 75% (3 out of 4) probability (see inheritance chart at top of page) of the mutated gene being inherited by an offspring. Even if a child does not have beta thalassemia major or intermedia, they can still be a carrier, possibly resulting in future generations of their offspring having beta thalassemia.

Another risk factor is ancestry. Beta thalassemia occurs most often in people of Italian, Greek, Middle Eastern, Southern Asian, and African ancestry.

Diagnosis

Peripheral blood smear from a person with beta thalassemia. The red blood cells vary greatly in shape and size and some look empty because of their low hemoglobin content. (Giemsa stain)

Abdominal pain due to hypersplenism, splenic infarction and right-upper quadrant pain caused by gallstones are major clinical manifestations. However, diagnosing thalassemia from symptoms alone is inadequate. Physicians note these signs as associative due to this disease's complexity. The following associative signs can attest to the severity of the phenotype: pallor, poor growth, inadequate food intake, splenomegaly, jaundice, maxillary hyperplasia, dental malocclusion, cholelithiasis, systolic ejection murmur in the presence of severe anemia and pathologic fractures. Based on symptoms, tests are ordered for a differential diagnosis. These tests include complete blood count; hemoglobin electrophoresis; serum transferrin, ferritin, total iron-binding capacity; urine urobilin and urobilogen; peripheral blood smear, which may show codocytes, or target cells; hematocrit; and serum bilirubin. The expected pattern on hemoglobin electrophoresis in people with beta-thalassemia is an increased level of hemoglobin A2 and slightly increased hemoglobin F. The diagnosis is confirmed with hemoglobin electrophoresis or high performance liquid chromatography.

Skeletal changes associated with expansion of the bone marrow:

• Chipmunk facies: bossing of the skull, prominent malar eminence, depression of the bridge of the nose, tendency to a mongoloid slant of the eye, and exposure of the upper teeth due to hypertrophy of the maxillae.
• Hair-on-end (or "crew cut") on skull X-ray: new bone formation due to the inner table.

DNA analysis

All beta thalassemias may exhibit abnormal red blood cells, a family history is followed by DNA analysis. This test is used to investigate deletions and mutations in the alpha- and beta-globin-producing genes. Family studies can be done to evaluate carrier status and the types of mutations present in other family members. DNA testing is not routine, but can help diagnose thalassemia and determine carrier status. In most cases the treating physician uses a clinical prediagnosis assessing anemia symptoms: fatigue, breathlessness and poor exercise tolerance. Further genetic analysis may include HPLC should routine electrophoresis prove difficult.

Prevention

Beta thalassemia is a hereditary disease allowing for a preventative treatment by carrier screening and prenatal diagnosis. It can be prevented if one parent has normal genes, giving rise to screenings that empower carriers to select partners with normal hemoglobin. A study aimed at detecting the genes that could give rise to offspring with sickle cell disease. Patients diagnosed with beta thalassemia have MCH ≤ 26 pg and an RDW < 19. Of 10,148 patients, 1,739 patients had a hemoglobin phenotype and RDW consistent with beta thalassemia. After the narrowing of patients, the HbA2 levels were tested presenting 77 patients with beta thalassemia. This screening procedure proved insensitive in populations of West African ancestry because of the indicators has high prevalence of alpha thalassemia. Countries have programs distributing information about the reproductive risks associated with carriers of haemoglobinopathies. Thalassemia carrier screening programs have educational programs in schools, armed forces, and through mass media as well as providing counseling to carriers and carrier couples. Screening has shown reduced incidence; by 1995 the prevalence in Italy reduced from 1:250 to 1:4000, and a 95% decrease in that region. The decrease in incidence has benefitted those affected with thalassemia, as the demand for blood has decreased, therefore improving the supply of treatment.

Treatment

Beta thalassemia major

Surgically removed spleen of a Thalassemic child. It is about 15 times larger than normal.

Affected children require regular lifelong blood transfusions. Bone marrow transplants can be curative for some children. Patients receive frequent blood transfusions that lead to or potentiate iron overload. Iron chelation treatment is necessary to prevent damage to internal organs in cases of iron overload. Advances in iron chelation treatments allow patients with thalassemia major to live long lives with access to proper treatment. Popular chelators include deferoxamine and deferiprone.

The oral chelator deferasirox was approved for use in 2005 in some countries. Bone marrow transplantation is the only cure and is indicated for patients with severe thalassemia major. 

Transplantation can eliminate a patient's dependence on transfusions. Absent a matching donor, a savior sibling can be conceived by preimplantation genetic diagnosis (PGD) to be free of the disease as well as to match the recipient's human leukocyte antigen (HLA) type.

Serum ferritin (the storage form of iron) is routinely measured in those with beta thalassemia to determine the degree of iron overload; with increased ferritin levels directing the use of iron chelation therapy. The three iron chelators; subcutaneous deferoxamine, oral deferiprone and oral deferasirox can be used as monotherapy or in combination, they have all been shown to decrease serum/systemic iron levels, hepatic and cardiac iron levels as well as decreasing the risk of cardiac arrhythmia, heart failure and death. Hepatic and myocardial MRI is also used to quantify the iron deposition in target organs, especially the heart and liver, to guide therapy.

Scientists at Weill Cornell Medical College have developed a gene therapy strategy that could feasibly treat both beta-thalassemia and sickle cell disease. The technology is based on delivery of a lentiviral vector carrying both the human β-globin gene and an ankyrin insulator to improve gene transcription and translation, and boost levels of β-globin production.

Surgical

Patients with thalassemia major are more inclined to have a splenectomy. The use of splenectomies have been declining in recent years due to decreased prevalence of hypersplenism in adequately transfused patients. Splenectomy is also associated with increased risk of infections and increased morbidity due to vascular disease, as the spleen is involved in scavenging to rid the body of pathologic or abnormal red blood cells. Patients with hypersplenism are more likely to have a lower amount of healthy blood cells in their body than normal and reveal symptoms of anemia. The different surgical techniques are the open and laparoscopic method. The laparoscopic method requires longer operating time but a shorter recovery period with a smaller and less prominent surgical scar. If it is unnecessary to remove the entire spleen a partial splenectomy may occur; this method preserves some of the immune function while reducing the probability of hypersplenism. Those undergoing splenectomy should receive an appropriate pneumococcal vaccine at least 1 week (preferably 3 weeks) before the surgery.

Therapeutic

Long-term transfusion therapy (in those with transfusion dependent beta thalassemia) is a treatment used to maintain hemoglobin levels at a target pre-transfusion hemoglobin level of 9-10.5 g/dL (11-12 g/dL in those with concomitant heart disease). To ensure quality blood transfusions, the packed red blood cells should be leucoreduced. By having leucoreduced blood packets, the patient is at a lower risk to develop adverse reactions by contaminated white cells and preventing platelet alloimmunisation. Patients with allergic transfusion reactions or unusual red cell antibodies must receive washed red cells or cryopreserved red cells. Washed red cells have been removed of plasma proteins that would have become a target of the patient's antibodies allowing the transfusion to be carried out safely. Cryopreserved red cells are used to maintain a supply of rare donor units for patients with unusual red cell antibodies or missing common red cell antigens. These regular transfusions promote normal growth, physical activities and suppress bone marrow hyperactivity.

Pharmaceutical

During normal iron homeostasis the circulating iron is bound to transferrin. But with iron overload (such as with frequent blood transfusions), the ability for transferrin to bind iron is exceeded and non-transferrin bound iron accumulated. This unbound iron is toxic due to its high propensity to induce oxygen species and is responsible for cellular damage. The prevention of iron overload protects patients from morbidity and mortality. The primary aim is to bind to and remove iron from the body and a rate equal to the rate of transfusional iron input or greater than iron input. Iron chelation is a medical therapy that may prevent the complications of iron overload. Every unit of transfused blood contains 200–250 mg of iron and the body has no natural mechanism to remove excess iron. The excess iron can be removed by iron chelators (deferoxamine, deferiprone and deferasirox).

Luspatercept (ACE-536) is a recombinant fusion protein that is used as a treatment in adults with transfusion dependent beta thalassemia. It consists of a modified extra-cellular domain of human activin receptor type IIB bound to the Fc portion of the human IgG1 antibody. The molecule binds to select transforming growth factor beta superfamily ligands to block SMAD2 and 3 signaling, thus enhancing erythroid maturation. The medication has been shown to reduce the transfusion burden by 33% in adults with transfusion dependent beta thalassemia as compared to placebo and was also associated with decreased ferritin levels (with no significant decreases in liver or cardiac iron levels).

Beta thalassemia intermedia

Patients with beta thalassemia intermedia require no transfusions or may require episodic blood transfusions during certain circumstances (infection, pregnancy, surgery). Patients with frequent transfusions may develop iron overload and require chelation therapy. Transmission is autosomal recessive; however, dominant mutations and compound heterozygotes have been reported. Genetic counseling is recommended and prenatal diagnosis may be offered.

Beta thalassemia minor

Patients with beta thalassemia minor are usually asymptomatic and are often monitored without treatment. Beta thalassemia minor may coexist with other conditions such as chronic hepatitis B, chronic hepatitis C, non-alcoholic fatty liver disease and alcoholic liver disease that, when combined or co-existing, may cause a person to have iron overload of the liver and more severe liver disease.

Epidemiology

The beta form of thalassemia is particularly prevalent among the Mediterranean peoples and this geographical association is responsible for its naming: thalassa (θάλασσα) is the Greek word for sea and haima (αἷμα) is the Greek word for blood. In Europe, the highest concentrations of the disease are found in Greece and the Turkish coastal regions. The major Mediterranean islands (except the Balearics) such as Sicily, Sardinia, Corsica, Cyprus, Malta and Crete are heavily affected in particular. Other Mediterranean peoples, as well as those in the vicinity of the Mediterranean, also have high incidence rates, including people from West Asia and North Africa. The data indicate that 15% of the Greek and Turkish Cypriots are carriers of beta-thalassaemia genes, while 10% of the population carry alpha-thalassaemia genes.

Evolutionary adaptation

The thalassemia trait may confer a degree of protection against malaria, which is or was prevalent in the regions where the trait is common, thus conferring a selective survival advantage on carriers (known as heterozygous advantage), thus perpetuating the mutation. In that respect, the various thalassemias resemble another genetic disorder affecting hemoglobin, sickle-cell disease.

Incidence

The disorder is more prevalent in certain ethnicities and age groups. Beta thalassemia is most prevalent in the "thalassemia belt" which includes areas in Sub-Saharan Africa, the Mediterranean extending into the Middle East and Southeast Asia. This geographical distribution is thought to be due to beta-thalassemia carrier state (beta thalassemia minor) conferring a resistance to malaria. In the United States, thalassemia's prevalence is approximately 1 in 272,000 or 1,000 people. There have been 4,000 hospitalized cases in England in 2002 and 9,233 consultant episodes for thalassemia. Men accounted for 53% of hospital consultant episodes and women accounted for 47%. The mean patient age is 23 with only 1% of consultants the patient is older than 75 and 69% were 15-59 year olds. It is estimated that 1.5% of the world's population are carriers and 40,000 affected infants are born with the disease annually. Beta thalassemia major is usually fatal in infancy if blood transfusions are not initiated immediately.