Transfusion Transmitted Disease

What is Transfusion Transmitted Disease?

Every year, almost 5 million people in America receive blood transfusions. These are needed for a variety of health concerns such as significant blood loss, surgeries, hemophilia, or cancer. Every day, nearly 29,000 units of red blood cells, 5,000 platelets, and 6,500 plasma units are used in the US. Still, there is a small risk of diseases being passed on through these transfusions. This mainly happens due to “window-period” donations. These are donations made during a period of time when the testing might not detect certain antibodies and antigens (proteins that trigger responses from your immune system), even though they might be present. In addition to this, there’s also a risk that the blood supply could be contaminated by unknown harmful microorganisms.

When receiving blood transfusions, there is a chance that they could contain harmful bacteria, viruses, and parasites. Of these, the chance of getting a bacterial infection from a transfusion is higher than that of a viral infection, especially for those receiving platelet transfusions. Transfusions can potentially transmit viruses such as HIV, hepatitis A, B, and C, West Nile virus, cytomegalovirus (a type of common virus), severe acute respiratory syndrome coronavirus (the cause of SARS), human T-cell lymphotropic viruses (types of viruses that can infect immune cells), Zika virus, and parvovirus B19 (which can cause a variety of illnesses).

There are also other harmful agents, called prions, which can cause Creutzfeldt-Jakob disease (a rare and fatal brain disorder), and protozoa, specifically of the Plasmodium genus, which can cause malaria. However, the safety of the blood supply is improving all the time due to advancements in testing methods, careful donor screening, and ways to inactivate pathogens, or harmful organisms. It is very important to keep being diligent about these procedures in order to deal with new emerging pathogens and improve current screening practices.

What Causes Transfusion Transmitted Disease?

Transfusion-transmitted bacterial infection (TTBI) usually occurs when bacteria are introduced into the bloodstream during a blood transfusion. The bacteria can contaminate the blood at different stages such as when the blood is collected, processed, stored, or during the transfusion itself. Sources of bacterial contamination can include the bacteria naturally present on the skin, contaminated equipment used to collect or store blood, and improper handling of the blood.

The kind of disease-causing bacteria found can change depending on the blood product. For example, blood collected for transfusion is usually stored at temperatures that range from 34 to 43 °F (1 to 6 °C), a condition favoring the growth of certain bacteria known as gram-negative rods. The most common type of bacteria found in collections of red blood cells (RBC) is Yersinia enterocolitica, which is often associated with severe infection following an RBC transfusion. Additional common bacteria include Pseudomonas fluorescens, Enterobacter, Serratia, and Escherichia coli.

On the other hand, platelet products stored at room temperature (about 68-75 °F or 20-24 °C) have the highest risk of bacterial contamination. Gram-positive bacteria are most commonly found in platelet products, with Streptococcus viridans, Streptococcus bovis, and beta-hemolytic streptococci being the most prevalent.

Syphilis, a sexually transmitted disease caused by the bacterium Treponema pallidum, can also be transmitted from a mother to her unborn baby or through blood transfusions. However, the risk of transmitting syphilis through blood transfusion has significantly decreased due to careful screening processes and improved testing methods.

Besides bacteria, other causes of blood-transmitted diseases can be viral or parasitic pathogens. Infectious agents and newly identified pathogens continue to pose challenges to the safety of the blood supply, making it necessary to constantly monitor and adjust screening processes.

Viruses, such as Hepatitis A, B, and C, the Human immunodeficiency virus (HIV), the Human T-lymphotropic virus (HTLV), the West Nile virus, Cytomegalovirus, Zika virus, the Severe acute respiratory syndrome coronavirus (SARS-CoV-1), and Parvovirus B19 can all be found in blood and transmitted via transfusion.

Parasites too, such as those causing Malaria, Chagas disease, and Babesiosis, can also infect blood and be transmitted via transfusion.

Finally, Prions, abnormal proteins that cause brain diseases known as transmissible spongiform encephalopathies, pose a theoretical risk for transmission through blood transfusions. Till now, only one form, variant Creutzfeldt-Jakob disease (vCJD), has been known to be transmitted this way.

Risk Factors and Frequency for Transfusion Transmitted Disease

Less than 15% of all deaths related to blood transfusion are due to infections. Over the years, we’ve made a lot of progress in minimizing the chances of transfusion-related infections, which means that blood transfusion has become safer.

• The chance of bacterial infection through platelets is estimated to be 1 in 5,000 and 1 in 30,000 for red blood cells. Despite this risk, not every bacterial contamination will result in illness, especially in patients with healthy immune systems. However, those with weakened immune systems are most vulnerable.
• Approximately 7.1 million adults aged 15 to 49 contracted syphilis globally in 2020. However, contracting syphilis from a blood transfusion is not common because cooling blood for 24 to 48 hours kills the bacteria that cause syphilis.
• About 36.7 million people lived with HIV or AIDS globally in 2016. However, the risk of getting HIV from a blood transfusion is tiny, ranging from 1 in 1-2 million units in the US to 1 in 1-5 million units in parts of Europe.
• Hepatitis affects millions of people worldwide and leads to many complications and deaths each year. Despite this, the risk of contracting Hepatitis B or C during a blood transfusion is very low.
• About 15 million people worldwide live with the Human T-lymphotropic virus I (HTLV-I), but the risk of transmitting it through blood transfusion per population is minimal at 1 in 2.7 million.
• The West Nile Virus is another potential risk, most likely to result in severe diseases in older individuals, but the presence of mosquitoes and wild birds primarily circulate it.
• Despite the high global occurrence of Cytomegalovirus (CMV) infections, the likelihood of getting CMV from a blood transfusion is sporadic.
• About 20% to 25% of people infected with the Zika virus show symptoms. Although no verified cases of Zika virus transmission via blood transfusion have been reported, some cases have been confirmed via platelet transfusion.
• No cases of the severe acute respiratory syndrome coronavirus (SARS-CoV-1) have been reported since 2004, but the risk of its reemergence still exists.
• Parvovirus B19 is widely prevalent, particularly in the US, where between 50% and 80% of adults have had an infection. Recipients receiving blood products created from large pools have a higher risk of contracting parvovirus than recipients who get blood products from a single donor.
• According to the World Health Organization, there were 247 million malaria cases worldwide and concentrated primarily in Africa. However, the risk of contracting malaria through a blood transfusion is less than 1 per 1 million units of blood in the US.
• Chagas disease is a significant issue in Latin America and impacts about 10 million people globally. A 13% risk used to be associated with platelet transfusion, but this has been reduced since introducing mandatory screening in the US.
• Babesiosis is a risk, primarily in the northeastern and upper Midwest of the US, in Europe and Asia, with more than 250 transfusion-transmitted cases reported to date.

Signs and Symptoms of Transfusion Transmitted Disease

Recognizing Transfusion-Transmitted Bacterial Infections (TTBI) can be challenging. Symptoms may show during or within 72 hours after the transfusion and may range from no symptoms to septic shock. Some of the signs that indicate a septic transfusion reaction include:

• Temperature greater than 102.2°F (39°C)
• A temperature increase of more than 3.6°F (2°C) within a few hours following transfusion
• Shaking chills
• Heart rate more than 120 beats per minute
• A heart rate increase of 40 beats per minute or more within a few hours after transfusion
• Changes in blood pressure levels by more than 30 mm Hg

Other potential symptoms include nausea, vomiting, abdominal pain, back pain, and hypothermia.

Syphilis, a sexually transmitted infection, initially appears as a painless ulcer around the genital, oral, or anal areas. If left untreated, it progresses through several stages. The secondary stage, occurring within 3 to 6 weeks, features a rash on the hands and feet, along with fever, weight loss, sore throat, patchy hair loss, headache, and muscle pain. Tertiary syphilis, which can occur 10 to 30 years post-infection, can affect the heart, blood vessels, brain, and more.

Hepatitis B and C, HIV, Human T lymphotropic virus I, West Nile virus, Cytomegalovirus, Zika virus, SARS-CoV-1, and Parvovirus B19 infections present a variety of symptoms ranging from none to severe, depending on the individual’s immune response and progression of the infection.

Malaria, Chagas disease, and Babesiosis are parasitic infections that show symptoms typically after some period of exposure. For example, symptoms of malaria usually show between 12 and 35 days after exposure, including high fevers, heavy sweating, chills, and headache. Similarly, Chagas disease and Babesiosis have their unique symptomatology, with Chagas disease showing two distinct phases – acute and chronic, and Babesiosis having an incubation period of 1 to 4 weeks after a tick bite.

Testing for Transfusion Transmitted Disease

Ensuring the safety of the blood supply is critical. For this reason, blood donation centers have thorough processes in place to check potential donors and the blood they donate. When you go to donate blood, you’ll be asked to complete an in-depth questionnaire. The questions will cover a range of topics, including any history of drug use, recent travel, current illnesses or medications, any history of HIV or hepatitis, and your vaccination history.

After donation, the blood undergoes further screening. It’s tested for a range of things, including various types of hepatitis, HIV, viruses such as Zika and West Nile, and certain types of harmful bacteria or parasites. If you live in certain states, your blood might also be tested for Babesia, an infection that can be spread by ticks.

For platelets, a type of blood cell, donation centers generally check for any bacterial contamination. If the tests don’t show any signs of bacteria growth after 24 to 36 hours, the platelets are released for use.

The blood is also tested for syphilis, a sexually transmitted disease, using assays (tests) that look for certain antibodies in the blood. These antibodies are substances the body produces to fight off infections and can stay in your system for a while, even if you’ve been treated for syphilis.

In developed countries, the blood donated is typically tested for hepatitis B virus (HBV) and hepatitis C virus (HCV). Specific tests look for evidence of these viruses or the body’s response to them. The blood is also screened for HIV, the virus that causes AIDS.

Blood donation centers also use tests to check for the West Nile virus and the Zika virus. These viruses can cause serious illnesses and are usually spread by mosquitoes. For certain other viruses, like cytomegalovirus (CMV), and another type of human T-lymphotropic virus (HTLV), the tests look for antibodies in the blood.

The blood can also be tested for parasites, like those that cause malaria or Chagas disease. Various methods are employed, including looking at blood samples under a microscope and using certain tests that can detect antibodies or genetic material of these parasites.

In summary, there’s a comprehensive system in place to ensure the safety of the blood supply. Both donors and their donations are checked thoroughly to prevent any diseases or infections from being transmitted through blood transfusions.

Treatment Options for Transfusion Transmitted Disease

Blood donation centres and hospitals play a crucial role in ensuring the safety of blood products. They keep sterility in check, carry out programs that track back donated blood, adopt pathogen inactivation techniques that kill harmful organisms in the blood, and avoid accepting donations from people who might jeopardize the safety of the blood supply. They also ensure their staff members are well-trained and informed about the protocols for safe blood collection and handling.

Donors need to be healthy and free from infection or any recent antibiotic use. Clearing the skin with chlorhexidine before drawing blood helps prevent any bacteria on the skin from getting into the blood sample. The first small portion of the collected blood is tested for potential diseases and bacteria to minimize the risk of transmission through the donated blood. If a patient experiences symptoms after a transfusion, the blood is subjected to further bacterial tests, and the patient is treated promptly with antibiotics and other necessary treatments.

Lookback programs enable the tracking of blood donations from a donor who initially tested negative for infections but later tested positive. This system informs any recipients of the blood products from that donor so they can seek medical attention, which helps prevent the spread of infectious agents.

Pathogen inactivation is a process that neutralizes harmful viruses, bacteria, and parasites in the blood, adding an extra layer of safety to blood donations. Various techniques are used, such as Solvent-Detergent method, Methylene blue, Synthetic Psoralen, Riboflavin, Leukodepletion, Heat pasteurization, and Nanofiltration. These help in keeping the blood safe by eliminating harmful pathogens, but different techniques work differently and have different potential side effects. Some, for instance, might not work against particular types of viruses or bacteria, or they may affect beneficial components of the blood.

There are also rules to ensure safety by deferring blood donations from certain people under specific circumstances. For example, people with a history of diseases like HIV, AIDS, hepatitis, Creutzfeldt-Jakob Disease (a rare brain disorder), Chagas Disease, or leishmaniasis (a disease spread by sandfly) cannot donate. Also, individuals taking preventative medication for HIV, or those who have been incarcerated for more than 72 hours, must wait before they can donate. Other temporary restrictions can also apply, for example, following a blood transfusion or after travel to certain areas.

What else can Transfusion Transmitted Disease be?

The main difficulty in diagnosing Transfusion-transmitted bacterial infections (TTBI) is distinguishing it from other reactions that could happen after a blood transfusion. Some other reactions also start with conditions like fever and chills. Here’s a brief of other reactions that physicians consider before diagnosing TTBI:

• Febrile non-hemolytic transfusion reaction: This begins with fever and chills but doesn’t come with additional symptoms. This condition is often only diagnosed after ruling out other possibilities.
• Acute hemolytic transfusion reaction: This is characterized by the quick breakdown of red blood cells that were transferred through the transfusion, often due to incompatibility between blood types. Typical symptoms include fever, chills, back pain, and bleeding from areas where the patient was injected.
• Transfusion-related acute lung injury: This manifests with fever, chills, and difficulty breathing which is usually caused by immune system responses triggered by the donated blood.
• Hypotensive transfusion reactions: This primarily presents as a significant drop in blood pressure without any apparent cause. The patient’s blood pressure typically returns to normal after the transfusion is halted.
• Preexisting infection: The symptoms could be linked to an infection that was present before the transfusion.
• Transfusion-associated graft versus host disease: This is a condition where the immune cells from the donated blood attack the patient’s tissues.

Doctors need to carefully evaluate these conditions before coming to a definitive diagnosis.

What to expect with Transfusion Transmitted Disease

The likelihood of recovering from Transfusion-Transmitted Disease (TTD) depends on several factors including the type of infectious agent that caused the disease, the quality and availability of healthcare in the individual’s location, and their immune health. Infections caused by certain types of bacteria referred to as gram-negative organisms lead to a higher possibility of death. In the US, there are typically 2 to 3 deaths annually due to Transfusion-Transmitted Bacterial Infection (TTBI).

With chronic Hepatitis B Virus (HBV), between 12% and 20% of patients worsen and develop cirrhosis, a serious liver disease. Of those who develop cirrhosis, around 20% experience serious liver failure known as hepatic decompensation, while 6% to 15% may develop liver cancer. The 5-year survival rate for patients with managed cirrhosis is 85%, but this significantly drops to 14%-35% for patients with decompensated cirrhosis.

In terms of Hepatitis C Virus (HCV) infection, 50% to 85% of patients can’t clear the infection and thus develop a chronic condition. Over 20 to 30 years, 5% to 30% of these chronic HCV patients develop cirrhosis. Every year in the US, between 8000 and 13000 deaths are attributed to HCV.

Without drugs to manage Human Immunodeficiency Virus (HIV), the average life expectancy after infection is just 12 to 18 months. However, starting antiretroviral therapy can substantially extend one’s life expectancy to near-normal.

West Nile Virus (WNV) mainly leads to severe outcomes in patients developing neuroinvasive disease – a condition that affects the brain or the spine. Death rates have been estimated at 2% for patients with meningitis (an infection of the lining around the brain and spine), 14% for those with encephalitis (inflammation of the brain), and 13% in those with acute flaccid paralysis (a sudden paralysis). Meanwhile, the prognosis for malaria, another infectious disease, is generally favorable when treated properly. But globally, over 600,000 people die from malaria each year, most of whom are African children under five.

For adult T-cell leukemia-lymphoma, a type of cancer that affects the blood and lymph system, survival rates can vary. The acute form has an average survival of about 6 months, the chronic form has an average survival period of 2 years, while the smoldering form can lead to survival up to 5 years.

For chronic Chagas disease, a parasitic infection, most deaths are related to the heart being affected. The annual death rate for any cause in patients with Chagas is 7.9%, and the yearly death rate specifically due to heart-related issues is 6.3%.

Possible Complications When Diagnosed with Transfusion Transmitted Disease

The complications of Transfusion Transmitted Diseases (TTD) are determined by the specific disease that is transmitted. Let’s break down these complications by the type of disease:

West Nile Virus:

• Chorioretinitis: an inflammation of the eye that can impair vision
• Retinal hemorrhages: bleeding in the eyes
• Vitreitis: inflammation of the jelly-like substance inside the eye
• Rhabdomyolysis: a serious condition due to muscle injury
• Fatal hemorrhagic fever with organ failure
• Hepatitis and pancreatitis
• Issues with the nerves (brachial plexopathy, demyelinating neuropathy, motor axonopathy) including Guillain-Barré syndrome-like symptoms
• Inflammation of the heart muscle, testicles, and muscles
• Conditions causing muscle weakness like myasthenia gravis

HIV:

• Opportunistic infections
• Cancers or malignancies
• Progression to AIDS
• Death

Hepatitis B and C:

• Chronic hepatitis
• Liver failure
• Cirrhosis or scarring of the liver
• Liver cancer
• Variceal hemorrhage or bleeding from swollen veins in the esophagus
• Encephalopathy or brain disease
• Death

Cytomegalovirus:

• Congenital CMV: the baby is born with the virus
• Various organ inflammations (enteritis, colitis, hepatitis, etc.)
• Rejection of transplanted organs
• Inflammations targeting the brain or its linings (meningitis, encephalitis)

Syphilis:

• Aortitis or inflammation of the aorta
• Gummatous disease
• General paresis, or muscle weakness
• Tabes dorsalis, a form of neurosyphilis
• Meningitis or inflammation of the meninges

Zika Virus:

• Guillain-Barré syndrome
• Encephalitis or brain inflammation
• Meningoencephalitis or inflammation of the brain and meninges
• Brain ischemia or reduced blood flow to the brain
• Neuropsychiatric and cognitive symptoms

Chagas Disease:

• Muscle atrophy or the wasting of muscles
• Heart failure
• Megaesophagus and Megacolon: abnormally large esophagus or colon
• Heart rhythm problems and esophageal diseases

Malaria:

• Acute respiratory distress syndrome
• Seizures and Coma
• Severe anemia: a decrease in red blood cells
• Hypoglycemia or low blood sugar
• Multiple organ failure
• Death

Babesiosis:

• Acute respiratory distress syndrome
• Congestive heart failure
• Severe anemia
• Renal or kidney failure
• Coma
• Disseminated intravascular coagulation: a condition that causes clots and bleeding
• Death

Preventing Transfusion Transmitted Disease

The blood supply in the United States is known to be very safe. However, there is a small chance that diseases can be spread through transfusions, where blood is given from one person to another. These diseases can be caused by different types of organisms including bacteria, viruses, prions (a type of protein that can cause disease), and parasites. To lower this risk as much as possible, certain steps are taken. These include asking donors questions about their health and conducting laboratory tests. Also, a method called Pathogen Reduction Technology is used after blood is collected to provide extra protection against diseases that can be transmitted through transfusions.

Infections caused by parasites that are transmitted through transfusions are not common, but they can include diseases like babesiosis, Chagas disease, leishmaniasis, and malaria. To assess the risk of spreading these kinds of infections, donors are asked questions about any recent travel they’ve done. Viral diseases including Hepatitis A and B, Hepatitis C, HIV, Human T-Lymphotropic Virus, West Nile Virus, and Zika Virus can also be transmitted through transfusions. However, the chance of this happening is extremely low because of the thorough testing done on the blood supply. Prion diseases are rare disorders that damage the nervous system and they can also be transmitted by blood transfusion. The chance of getting a prion diseases like variant Creutzfeldt-Jakob disease (vCJD) from a transfusion is unclear, but steps are taken to lessen any risks as much as possible.

It’s important for patients to know about these risks before getting a blood transfusion. They should be involved in the screening process and follow any guidelines given by their doctors or nurses. People who donate blood have to meet certain requirements and there are also waiting periods between donations to help prevent the spread of infections. All of the rules for donating blood can be found on the Red Cross’ website here: https://www.redcrossblood.org/donate-blood/how-to-donate/eligibility-requirements/eligibility-criteria-alphabetical.html.