Transfusion Transmitted Disease


Article Author:
Angel Justiz Vaillant


Article Editor:
Kristin Sticco


Editors In Chief:
William Gossman


Managing Editors:
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Carrie Smith
Abdul Waheed
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Radia Jamil
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Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
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John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
6/18/2019 6:26:43 PM

Introduction

About 5 million Americans require a blood transfusion each year, needed for acute blood loss, surgery, hemophilia or cancer. Transfusion transmitted-diseases (TTD) comprise several pathologies that are transmitted by blood transfusions. The various biological agents involved are mainly viruses and parasites. For example, microorganisms such as hepatitis B virus and HIV-1 can be transmitted by a contaminated blood transfusion from an infected individual to a recipient and cause disease that can lead to chronic hepatitis and acquired immunodeficiency syndrome respectively. A list of TTD includes infections caused by human T-lymphotropic virus 1, cytomegalovirus and West Nile virus, severe acute respiratory syndrome (SARS), malaria, Chagas disease, babesiosis, leishmaniasis, variant Creutzfeldt-Jakob disease, Zika, Dengue, Chikungunya, and anaplasmosis.

Etiology

Hepatitis A is an infectious disease caused by the hepatitis A virus (HAV), which is a distinct member of the picornavirus family. HAV is a 27- to 32-nm spherical particle with cubic symmetry, contains a linear ssRNA genome that has a size of 7.5 kb.[1]      

Hepatitis B virus (HBV) causes the hepatitis B. HBV is a hepadnavirus and has a double-stranded DNA genome with a size of 3.2 kb.[2] 

Hepatitis C virus (HCV) causes hepatitis C. HCV is a member of the Flaviviridae family and is a 60-nm spherical particle, enveloped, and contains a single-stranded RNA genome with a size of 9.4 kb.[3]

HIV is a retrovirus that comprises two subtypes: HIV-1 that is the most prevalent worldwide and most common etiological agent of AIDS. HIV-2 that primarily affects West Africa.[4]

Human T-lymphotropic virus 1 (HTLV-1) is a human retrovirus well-known to cause adult T-cell leukemia/lymphoma and  HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP).[5][6]

Malaria is an infectious illness caused by parasites of the Plasmodium genus. It is primarily transmitted by bites of female mosquitoes of Anopheles species. It may transmit by blood transfusion collected from asymptomatic or parasitic donors with low parasite densities. Erythrocyte concentrate, along with fresh frozen plasma, cryoprecipitate and platelet concentrate are involved in the genesis of transfusion-transmitted malaria.[7]

Trypanosoma cruzi causes Chagas disease and is endemic in Latin America where it is primarily a problem in the context of blood transfusion transmission. Trypanosoma is a genus of kinetoplastids and belongs to a group of unicellular parasitic flagellate protozoa.[8]

West Nile virus infection (WNVI) is a vector-borne disease caused by West Nile virus (WNV), an enveloped ssRNA virus within the family Flaviviridae that impose a threat to many transfusion services worldwide.[9]

Epidemiology

It is estimated that 240 million individuals are chronically infected with hepatitis B virus. Of these cases, more than 680,000 individuals die every year due to complications of hepatitis B, including cirrhosis and liver cancer. Approximately 150 million individuals worldwide have chronic hepatitis C infection, and nearly 700,000 of them die each year from the liver disease.[3] Hepatitis B and C are prevalent worldwide, especially in HIV patients and in those on hemodialysis and with coagulation disorders.

The estimated number of humans living with HIV/AIDS is 36.7 million worldwide as of 2016. Other risk factors associated with a risk of acquiring HIV infection include men who have sex with men, unsafe sexual practices, the use of intravenous drugs, and hazardous blood transfusions or blood products.[10][11]

HTLV-1 exists in the blood of 15 million people, which are chronically infected worldwide. HTLV-1 is transmitted sexually, perinatally (breastfeeding), and parenterally (blood transfusions, injection drug user, and transplants).[6]

The African continent has seen a long-term decline in the prevalence of malaria caused by Plasmodium falciparum from 40% (1900 through 1929) to 24% prevalence (2010 through 2015), this result has been interrupted by a time of rapidly increasing or decreasing transmission.[12] The WHO reported that in 2016 there were an estimated 216 million cases of malaria worldwide.

Chagas disease is currently a public health problem in Latin America. The vector-borne transmission is the most critical mode for this disease, but other ways such as transfusions require further epidemiological study. Thus in Colombia, the frequency of T. cruzi was serologically low, but it may vary among other nations in the region.[13] An estimated 10 million people are infected worldwide and mostly in Latin America.[14] 

There are many pathogenic isolates of WNV, but the two major WNV lineages L1 and L2 are responsible for most outbreaks observed. L1 includes strains from North, Central and South America, Africa and the Middle East and L2 covers from sub-Saharan Africa, Madagascar, and Eastern Europe, where it has become endemic. An independent L2 strain, detected in 2004 in Southern Russia, caused outbreaks of West Nile neuroinvasive disease in Romania since 2010. This virus circulates primarily between wild birds and mosquitos. Transmission among humans exists through blood transfusion, intrauterine exposure, breastfeeding, and organ transplantation.[9]  Only 1 in 150 WNVI results in severe neurologic illness, and often an elderly.

History and Physical

Viral hepatitis B and C are characterized by:

  • Tiredness
  • Sore muscles
  • Nausea
  • Vomiting
  • Diarrhea
  • Jaundice
  • Fever
  • Dark urine
  • Clay-colored stools
  • Abdominal pain

Primary HIV infection occurs 4 to 10 weeks after unsafe sexual practice with an HIV-infected person or a hazardous blood transfusion.[10] The following symptoms characterize the primary HIV infection:

  • Fever
  • Joint pain
  • Skin rash 
  • A sore throat
  • Tiredness
  • Swollen lymph nodes

Chronic HIV disease leads to AIDS, which has a high mortality rate due to opportunistic infections and malignant tumors.[10]

Human T lymphotropic virus 1 (HTLV-1) causes adult T-cell leukemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP).[15][16] The first one is a lymphoproliferative disorder and the second one characterizes by an insidious onset and chronicity. Initial symptoms of TSP include:

  • Gait problems 
  • Low back pain  
  • Unexplained falls  
  • Constipation  
  • Urinary urgency/incontinence
  • Numbness or pain in the lower limbs

On the physical examination patient  with TSP may have:

  • Hyperreflexia in both knees
  • Ankle clonus bilaterally
  • Spasticity in both lower extremities

Malaria often presents with:

  • Severe shaking chills
  • High fever
  • A headache
  • Profuse sweating
  • Nausea
  • Vomiting 
  • Abdominal pain
  • Diarrhea
  • Convulsions
  • Coma
  • Bloody stools
  • Anemia

The Chagas disease presents with acute, intermediate and chronic symptoms and signs.[17] Acute infection presents with:

  • Chagoma  
  • Rash 
  • Lymph nodes enlargement
  • A headache and body aches 
  • Fever 
  • Fatigue 
  • Gastrointestinal symptoms including nausea, vomiting, and diarrhea 
  • Hepatomegaly 
  • Splenomegaly 
  • Romana's sign

The chronic phase of the Chagas disease presents with:

  • Irregular heartbeats 
  • ECG changes 
  • Fainting 
  • Palpitations 
  • Chronic abdominal pain 
  • Chronic constipation 
  • Dilated colon  
  • Shortness of breath 
  • Cardiomyopathy 
  • Congestive heart failure  
  • Emphysema 
  • Stroke  
  • Sudden death

West Nile virus infection may present with some of the following signs and symptoms:

  • Fever
  • A headache
  • Body aches
  • Skin rash
  • Swollen lymph nodes
  • Stiff neck
  • Sleepiness
  • Coma
  • Convulsions
  • Paralysis

Evaluation

Transfusion-transmitted HBV infection is currently prevented in most developed countries by testing for HBV surface antigen (HBsAg), nucleic acid testing (NAT), and screening for antibodies against the HBV core antigen.[2] Nucleic acid testing (NAT) for HIV and HCV has been implemented in several European nations and the United States. NAT implementation has improved the safety of blood donations by reducing the risk of infectious units per million donations.[18] 

In Brazilian blood banks, the testing of Plasmodium falciparum relies on blood thick smears examination. A study was conducted to demonstrate that molecular biology techniques can be more efficient in detecting Malaria among blood donors. The molecular diagnostic based on mitochondrial DNA using real-time PCR (mt-qPCR) was improved to detect P. falciparum, Plasmodium vivax, and Plasmodium malariae. The analytic sensitivity of this mt-qPCR test showed to be highly efficient and effective in revealing potentially infected donors and should be applied as a screening routine of asymptomatic carriers for the prevention of transfusion-transmitted malaria in blood banks.[7]   

The frequent occurrence of inconclusive serology affecting blood banks and the lack of a standard gold test for Chagas disease led to study the efficacy of the blood culture test and other commercial tests based on enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence and hemagglutination assay. These methods were useful in testing for anti-Trypanosoma cruzi antibodies and predict the absence of infection with a probability of 100% when using in combination.[14]

Several methods are being used to reduce infectivity of blood products, e.g., solvent-detergent processing of plasma and also nucleic acid cross-linking via photochemical reactions with riboflavin, methylene blue,  psoralen, and alkylating agents.[19]

Treatment / Management

Hepatitis B and C

Hepatitis B: The treatment of viral hepatitis B includes general management (bed rest and abstaining from alcohol). Hepatitis B is treated with drugs, such as adefovir dipivoxil and lamivudine.[20]

Hepatitis C: The current treatment of choice for HCV infection (chronic) is a combination of ribavirin and pegylated interferon alfa.[21]

Human immunodeficiency virus infection: The treatment of choice for HIV infections is antiretroviral therapy (ART). For example, the use of one of the following combinations: abacavir/dolutegravir/lamivudine (Triumeq), or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild).[10]

HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP): Use of corticosteroids, plasmapheresis, cyclophosphamide, and interferon temporarily alleviate signs and symptoms associated with HAM/TSP.[22] Mogamulizumab (a defucosylated humanized anti-CCR4 IgG1 antibody), is under investigation for the treatment of HAM/TSP.

Malaria: Quinine is the drug of choice for malaria. A second agent in drug-resistant P. falciparum is doxycycline, tetracycline, clindamycin or pyrimethamine-sulfadoxine.[23]

Chagas disease: Benznidazole and nifurtimox are of benefit as drugs of choice for American trypanosomiasis.[24][25]

West Nile virus infection: No specific antiviral treatments or vaccine is available for West Nile virus infection. Supportive therapy is given to severe cases.

Differential Diagnosis

Hepatitis B: The treatment of viral hepatitis B includes general management (bed rest and abstaining from alcohol). Hepatitis B is treated with drugs, such as adefovir dipivoxil and lamivudine.[20]

Hepatitis C: The current treatment of choice for HCV infection (chronic) is a combination of ribavirin and pegylated interferon alfa.[21] 

Human immunodeficiency virus infection: The treatment of choice for HIV infections is antiretroviral therapy (ART). For example, the use of one of the following combinations: abacavir/dolutegravir/lamivudine, or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate.[10]

HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP): Use of corticosteroids, plasmapheresis, cyclophosphamide, and interferon temporarily alleviate signs and symptoms associated with HAM/TSP.[22]  Mogamulizumab (a defucosylated humanized anti-CCR4 IgG1 antibody), is under investigation for the treatment of HAM/TSP.

Malaria: Quinine is the drug of choice for malaria. A second agent in drug-resistant P. falciparum is doxycycline, tetracycline, clindamycin or pyrimethamine-sulfadoxine.[23]

Chagas disease: Benznidazole and nifurtimox are of benefit as drugs of choice for American trypanosomiasis.[24][25]

West Nile virus infection: No specific antiviral treatments or vaccine is available for West Nile virus infection. Supportive therapy is given to severe cases.

Prognosis

TTD prognosis is mostly guarded depending on the type of disease transmitted to a recipient. HIV, hepatitis B and C, malaria and Chagas disease affects millions of people in the developing world and many unable to have access to healthcare. West Nile virus infection may be mild and may not need medical attention.

Complications

Malaria

  • Cerebral malaria 
  • Pulmonary edema  
  • Multi-organ failure  
  • Anemia.

HIV Infection

  • Opportunistic infections  
  • Several malignancies

Hepatitis B and C

  • Chronic hepatitis  
  • Liver failure   
  • Cirrhosis    
  • Hepatocellular carcinoma of the liver

Chagas disease

  • Muscle atrophy
  • Heart failure 
  • Megaesophagus
  • Megacolon

Pearls and Other Issues

  • Cytomegalovirus (CMV) is transmitted by transfusion of blood products. It causes severe disease in immunosuppressed individuals, including transplant recipients and neonates.[26]
  • A protozoan of the genus Babesia causes babesiosis, that is transmitted by ixodid tick vectors, which feed blood from the host. Babesia can be transmitted through a blood transfusion among humans. This zoonosis is endemic primarily in the upper Midwestern and Northeast United States. Babesia can replicate in the host’s erythrocytes that are called piroplasms due to their pear-shaped appearance within the red blood cells.[27]
  • Transfusion-transmitted leishmaniasis is a concern in endemic regions. Donors should be tested for leishmaniasis using immunofluorescent antibody test, PCR, ELISA, and leishmaniasis rapid test. Blood bank should be aware of the threat that imposes leishmania-contaminated blood and should routinely include a test to diagnose this infection.[28]
  • Variant Creutzfeldt-Jakob disease is a transmissible spongiform encephalopathy (a proteinopathy) usually associated with deposits of abnormal prion protein in the brain. Symptoms include behavioral and psychiatric problems. Blood transfusions can transmit this disease.[29]
  • Zika is an infectious disease caused by Zika virus, which has recently emerged as a cause of outbreaks in many countries. The clinical picture of Zika is variable from primarily mild exanthematic febrile disease to microcephaly and Guillain-Barre Syndrome. Mosquito of the Aedes type usually transmit Zika virus, but transmission through transfusion of blood products has been reported in French Polynesia and Brazil.[30] Dengue and Chikungunya are TTD transmissible by the same mosquito that causes Zika.
  • A blood transfusion can transmit human granulocytic anaplasmosis (HGA). It is a tick-borne rickettsial infectious disease. The clinical picture of anaplasmosis includes a headache, fever, and chills. The HGA diagnosis is made by the presence of polymorphonuclear leukocytes containing morulae in the peripheral smear. Samples from the recipient may test positive by PCR for Anaplasma phagocytophilum.[31] 
  • Bacterial sepsis is one of the transfusion-transmitted diseases. The prevalence of bacterial contamination in red blood cells and platelets is approximately 1 in 3000 units transfused.[32]

Enhancing Healthcare Team Outcomes

All healthcare workers who transfuse blood and related products must be fully aware of the diseases that can be transmitted. In North America, most hospitals have guidelines for blood transfusions, and these protocols must be observed. While blood transfusions have become safer compared to the past, clerical errors either in the laboratory or at the nurse's end often result in transfusion complications. There is no substitute for constant vigilance and monitoring during and after a blood transfusion.

TTD prognosis is mostly guarded depending on the type of disease transmitted to a recipient. HIV, hepatitis B and C, malaria, and Chagas disease affects millions of people in the developing world and many unable to have access to healthcare. West Nile virus infection may be mild and may not need medical attention.


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Transfusion Transmitted Disease - Questions

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As per the FDA regulations, plasma undergoes a battery of tests to identify which one of the following is a transfusion-transmitted disease?



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A blood transfusion can transmit which of the following microorganisms?



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Which of the following test is lease useful to diagnose a transfusion-transmitted disease?



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An 18-year-old male was in a motor vehicle collision, and 2 unit of whole blood were transfused at the emergency department of the nearest hospital. He was surgically treated and sent home under prescription. Two months after the accident he felt sick. He started complaining flu-like symptoms, fever and his family doctor found neck lymphadenopathy and a skin rash. What is the following step to follow this case?



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A 45-year-old patient presents with new-onset abdominal pain accompanied by fever, weakness, fatigue, joint pain, and loss of appetite. The patient reports that his urine is dark. He also complains of yellowish skin and mucosa for 1 week. Which question would not be helpful in clarifying the possible cause of his condition?



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Transfusion Transmitted Disease - References

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