Abstract
Immunodeficiency disorders are disorders characterized by a dysfunctional immune system. The immune system is the body’s defense against pathogens therefore a deficient immune system requires special interventions to keep affected patients protected from infection. Severe combined immunodeficiency (SCID) is a primary immunodeficiency disease. It is a rare and a serious life-threatening genetic condition. Patients with SCID do not have a well working immune system. Early diagnosis of this condition has a better chance of a long, healthy life for the SCID affected population. However, not all newborns are routinely screened for SCID. Undiagnosed infants with SCID are high risk for infection, either from exposure or through the administration of live vaccines. An ethical concern for SCID patients is administering live vaccines to undiagnosed infants. The ANA Code of Ethics should be applied in the care plans for all newborns to be screened for SCID to ensure effective and ethical care.
Key words: SCID, immune system, screening, ethics, vaccines
The Need to Screen for Bubble Boy Disease
Severe combined immunodeficiency (SCID) is the most severe form of inherited primary immunodeficiency (Gaspar, Hammarström, Mahlaoui, Borte, & Borte, 2014). The immune system is the body’s defense system and is vital in protection against infectious disease. Aside from the nervous system, the immune system is the most complex system the human body has. Many infectious and communicable diseases can be prevented with vaccinations. Vaccinations stimulate the immune system in healthy people to create memory and protection from specific infectious organisms. However, vaccinations are contraindicated in those who are immunosuppressed because certain vaccines contain live forms of the virus. Those affected by the inherited disorders of SCID do not have a well working immune system so they are susceptible to the potentially fatal effects of bacteria, viruses, and fungi (NIH, 2014). SCID is a condition that needs immediate diagnosis and treatment because of the susceptibility of those affected to life-threatening infections which could be prevented with screening at birth. The ANA Code of Ethics provision 1.3 “The Nature of Health” (p. 2) states that nurses are leaders who actively participate in assuring the responsible and appropriate use of interventions in order to optimize the health and well-being of those in their care. Administering live vaccinations to undiagnosed infants with SCID becomes an ethical issue because it is essentially injecting the virus into a person with no means to fight it or create immunity (Ballard, 2018). It is crucial to screen all newborns for SCID so this rare and life-threatening condition can be identified and treated with the appropriate healthcare interventions to advocate for the vulnerable population affected.
Immunodeficiency disorders cause partial or full impairment of the immune system. There are two categories of immunodeficiency disorders, primary and secondary. Primary immunodeficiency diseases are usually inherited and caused by a genetic mutation and are rare, life-threatening conditions. Secondary immunodeficiency diseases are the result of environmental factors that weaken the immune system. The most common secondary immunodeficiency disease is acquired immune deficiency syndrome (AIDS) which is caused by an environmental factor, the viral infection, HIV (British Society for Immunology, 2017). SCID falls under the category of primary immunodeficiency diseases (PID). PID are a group of more than 350 rare, chronic disorders affecting the body’s immune system (Immunodeficiency Foundation, 2018). These disorders are characterized by missing parts of an immune system or an improperly functioning immune system. SCID is one of the most severe types of PID.
The immune system is a network composed of cells, tissues, and organs. The cells that make up the immune system are lymphocytes that develop in the bone marrow in the form of stem cells. Stem cells develop into B-lymphocytes, T-lymphocytes, NK-lymphocytes, and phagocytes. These primary cells create antibodies against foreign antigens and attack and kill other harmful foreign invaders to the body (Ballard, 2018). The cells of the immune system are the body’s first line of defense against infection and recognize and destroy harmful pathogens. Pathogens can rapidly evolve and adapt, but cells that make up the immune system each have a different job in protecting the body from harmful pathogens. T-lymphocytes develop in the thymus after they become stem cells from the bone marrow (Alberts B., Johnson A., Lewis J., et al, 2002). The two main types of T-cells have different jobs, cytotoxic T cells kill infected cells, and helper T cells activate other cells of the immune system, including B cells.
SCID is a prenatal disorder of T-lymphocyte development and is already present at birth (Cossu, 2010). The absence of T-lymphocytes causes a lack of B-lymphocyte function and differentiation of NK-lymphocytes, or natural killer cells. There are no T-cells to kill pathogens or alert the other cells of the immune system, like B-cells, of the pathogens. SCID usually does not show any clinical signs or symptoms in affected newborns, even though they are born without any T-lymphocytes (Cossu, 2010). The dysfunctional immune system of SCID affected infants will cause them to acquire multiple, persistent and severe viral, bacterial, and fungal infections shortly after birth and rarely reach their first birthday (Cossu, 2010). Some of the specific clinical manifestations that would cause a baby to be evaluated for SCID are eight or more ear infections (otitis media), two or more cases of pneumonia, infections that do not resolve with antibiotic treatment for two or more months, failure to gain weight or grow normally, infections that require intravenous antibiotic treatment, deep-seated infections, such as pneumonia that affects an entire lung or an abscess in the liver, persistent thrush (Candida albicans) in the mouth or throat, or a family history of immune deficiency or infant deaths due to infections (National Human Genome Research Institute, 2014). Newborns are not exposed to these infections right away because they still have antibodies from their mothers that is passed down through the placenta, but these maternally transferred antibodies disappear by three months of age. Affected babies with SCID typically begin to require medical attention while presenting the clinical manifestations between three and six months of age (Allenspach E., Rawlings D.J., Scharenberg A.M., 2016). The pathophysiology of SCID requires prompt diagnosis and treatment before an opportunistic infection is acquired that can be fatal.
Numerous genetic mutations occur to the DNA of those affected with SCID (Cossu, 2010). According to the British Society of Immunology (2017), up to 70% of PIDs occur in males because many of the genes that mutate are linked to the X-chromosome (males have only one X chromosome compared with two in females, so a faulty gene on the female X chromosome is more likely to be masked by a working gene on the other X chromosome). Since females have two X chromosomes, if one X chromosome has the genetic mutation for SCID, the other X chromosome can compensate and overcome the genetic mutation and present normally. Males only have one X chromosome, so if the mother is a silent carrier of the mutation, then her male sons will have a 50% chance of expressing the mutated genes and her female daughters have a 50% chance of becoming silent carriers of the mutated genes as well. The X-linked gene that is altered is in IL2RG (Allenspach E., Rawlings D.J., Scharenberg A.M., 2016). The mutation in this gene causes the absence or almost complete absence of the T and NK cells, therefore causing nonfunctional B cells. Screenings of newborns affected by SCID include diagnostic testing that will show low absolute lymphocyte count compared to unaffected infants of the same age, low number of T cells, B cells can be present but are nonfunctional, and NK cells low or absent completely. DNA testing will show a mutation in the IL2RG coding region in more than 99% of affected males (IL2RG (Allenspach E., Rawlings D.J., Scharenberg A.M., 2016). A complete blood cell count, family history, and physical exam also are useful tools in diagnosing SCID.
Bubble Boy Disease is a nickname for SCID that became prominent in 1971. David Phillip Vetter, also known as Bubble Boy, was born on September 21, 1971 at Texas Children’s Hospital in Houston (CBS News, 2011). Twenty seconds after exposure to the outside world from his mother’s womb, newborn David was placed in a plastic, isolated sterilized bubble where he would spend most of his twelve years of life. David was able to survive despite his diagnosis of SCID for so long because of his sterile environment. Everything that went into his “bubble” had to be first sterilized in chambers filled with ethylene oxide gas, at a temperature of 140 degrees Fahrenheit, for four hours. Then, the items had to be aerated for one to seven days before they could enter the bubble (McVicker, 1997). Carol Ann Demaret, David’s mother, stated “Science was protecting David, this was never an experiment” (Immune Deficiency Foundation, 2018). David’s case had brought international attention to not only his life in the bubble, but to SCID. Newborns are not routinely screened for SCID therefore it is not caught until it is too late to intervene. In David Vetter’s case, he had an older brother who also had SCID, but died in infancy at age 7 months due to inability to fight infection. David’s mother Carol became pregnant with him shortly after the death of her first born son. There was a 50% chance of another SCID affected child because they were able to become aware of the X-linked genetic mutation because of his brother’s death, so plans were made on how to keep this child healthy until his immune system could be corrected (Ballard, 2018). David was able to be kept healthy from his bubble and created an opportunity for figuring out treatment for SCID patients. The only treatment for David at the time was a bone marrow transplant. In the United States, only two successful bone marrow transplants had been done before, and this was in 1968, just three years prior to David’s birth (Ballard, 2018). Only one of the two successful bone marrow transplants were for a SCID patient and the bone marrow donor was related to the patient and was a 100% match because they were related and Human Leucocyte Antigen (HLA) identical (Ballard, 2018). David had a sister who was not HLA identical, so David remained in his isolated sterilized environment until 1983, when according to the Immune Deficiency Foundation (2018), a technique was developed to use bone marrow from a donor who did not have to be a 100% match. When David was 12, his sister donated bone marrow. However, undetected traces of dormant Epstein-Barr virus, or mononucleosis, triggered cancer of the lymphatic system in the transplanted bone marrow David received. David Vetter died on February 22, 1984, 4 months after he received the bone marrow transplant. David’s mother Carol Ann had stated after his death “David was a great blessing to our family and to the world” (Immune Deficiency Foundation, 2018). David’s case brought national attention to the severity of SCID and the Texas Children’s Allergy and Immunology Clinic opened the David Center in his memory which provides state-of-the art care and cutting-edge research for primary immunodeficiencies (Texas Children’s Hospital, 2014). David’s legacy has led to further research and raised awareness to this pediatric emergency.
Since David’s case, other forms of treatment for SCID have been discovered and tested on SCID patients. Advances in bone marrow transplants and gene therapy are the treatment options available currently. The most effective treatment is still a bone marrow transplant, which takes stem cells from a healthy person’s bone marrow and transplants them into the bone marrow of a SCID patient (National Human Genome Research Institute, 2014). The bone marrow transplant is most effective with a matched sibling and at the youngest age possible, however this is not always available to SCID patients. Transplants can be performed from unmatched donors, like David’s sister’s donated bone marrow, but these types of transplants are less successful. All transplants done within the first three months of life have the highest success rate according to the National Human Genome Research Project. However, SCID often goes undiagnosed until at least three months of age since newborns and infants have antibodies from their mother until three months.
Two cases of X-linked SCID were being treated by gene therapy in April 2000, according to the Immune Deficiency Foundation. However, the insertion of the corrected DNA occurred next to a specific leukemia inhibitor, causing activation of leukemia in the patients. This devastating outcome of the gene therapy trial caused a hold on gene therapy for SCID worldwide (Immune Deficiency Foundation, 2018). Gene therapy is still an investigational treatment option that is not used unless a bone marrow transplant is not possible. Gene therapy is controversial due to the possible negative effects of inserting altered DNA back into the body and lack of successful trials. Although the first trials of gene therapy have failed, the National Human Genome Research Institute researchers are continuing to find a treatment that is successful in gene therapy. Their goal is to permanently correct the DNA of the T-cells without causing leukemia. They are also continuing to research bone marrow stem cells more thoroughly because the cells have life-saving qualities in SCID cases (National Human Genome Research Institute, 2014).
Treatment options for this rare but life threatening disorder are slim, but possible. Gene therapy is still being researched more thoroughly, but bone marrow transplants can succeed in correcting the immune system of an infant with the genetic disorder SCID. Newborn screening is vital in improving the health and outcomes for SCID patients. Early identification of SCID will help to determine the diagnosis appropriately and quickly, provide the correct healthcare interventions, and provide treatment to cure patients with SCID. The ANA Code of Ethics (2015) can relate specifically to the care for patients with genetic disorders. Members of the Ethics and Public Policy Committee of the International Society of Nurses in Genetics have applied to code of ethics for nurses to genetics and explain:
“As genetic/genomic information expands, and technologies become available, nurses in all areas of practice are being challenged to translate genetic/genomic knowledge into evidence-based practice as they educate, counsel, and support patients through the delivery of care. To effectively do so, nurses entering the workforce must be adequately informed about genetic/genomic concepts and emerging technologies” (Tluczek, A., et al, 2018).
Screening at birth will allow for SCID patients to live a long, healthy life outside of recurrent infection, failure to thrive, death, or life inside a bubble.
An ethical issue that SCID presents is the lack of intervention that is needed for the undiagnosed patients. SCID is estimated to affect about 40-100 babies in the United States each year, but because it is not routinely screened at birth the number of cases of SCID per year could be much higher. Although the U.S. Department of Health and Human Services recommended the addition of SCID to the uniform screening panel for all newborns (Cossu, 2010), it is still not being routinely screened in all states or worldwide. The Immune Deficiency Foundation has a Newborn Screening Campaign’s goal is to have every state as well as the District of Columbia, Navajo Nation, and Puerto Rico to include SCID on their newborn screening panel in order to save lives. If every newborn is screened at birth for SCID, then they can be diagnosed and treated in a timeframe that would allow them to be cured successfully. Diagnosis and treatment before the onset of infections and the complications they cause in immune-compromised babies reduces costly hospitalizations and leads to better outcomes. Testing immediately after birth can be done, either by sequencing DNA if the family mutation is known or by counting the numbers of T and B cells and assessing their function. National Human Genome Research Institute, 2014).
An ethical concern that SCID raises for nurses is the practice of administering vaccines. Vaccines are strongly recommended to be given throughout childhood and up to adolescence to protect and prevent the spread of diseases. Vaccines prevent many diseases that could be fatal to children. Forms of the infectious diseases are used in vaccines and injected into the body so the immune system can fight the disease and create immunity towards it, allowing protection in case of exposure to any of the harmful diseases that vaccines have come to prevent. Certain vaccines, like the Rotavirus and MMR vaccine, contain live forms of the virus. People with immunodeficiencies should not receive live vaccines because they do not have an adequate immune system to fight off or create protection against these live forms of disease. Because SCID is not routinely screened for, undiagnosed infants are receiving live forms of diseases and do not have the immunological means to fight off or build immunity to these infectious diseases. Exposing them to live forms of infectious disease is causing harm to these vulnerable infants. At 2 months old, infants typically receive their rotavirus vaccine and the MMR vaccine by 12 months. Healthcare providers should check if infants are screened for SCID before administering live vaccines that can infiltrate the impaired immune systems of these infants and give them the illness, causing direct harm to their health instead of protecting their health. Nursing interventions for patients with SCID should be adhering to all types of isolation precautions for their patients, performing adequate hand hygiene, and watching closely for signs or symptoms of infection. Nurses also should be sure to educate all their patients on the importance of vaccines. According to the Code of Ethics for Nurses (provision 2), “the nurse’s primary commitment is to the patient, whether an individual, family, group, community, or population.” (ANA, 2015). The SCID population, although rare, requires commitment from nurses. Nurses must commit to promoting and protecting the health of their patients. Patients with SCID require infection prophylaxis and a close monitoring of their immune system. Nurses must care for and support each patient according to their individual needs. Patients with SCID, although a life-threatening condition, do have a chance of a long, healthy life, through early diagnosis and treatment. All newborns should be screened for SCID because early diagnosis of this primary immunodeficiency disorder has a positive and successful outcome for the health and life of the affected child.