How Long Does Fecal Shedding Occur for Oral Vaccines?

Patient Presentation
A 78-day-old female came to clinic because her mother was concerned that her stools were “diarrheal.” She was breastfed and her mother said that her stools were “always loose.” For the past 3 weeks her stools were more frequent (4-5 times/day) of loose, pudding-like stools without blood, mucous or changes in color. They were yellow in color, and not foul-smelling nor voluminous. Her mother was concerned because her mother was visiting from another country and had had diarrhea. The baby was feeding well and acting well otherwise. The past medical history showed she was a full-term, first-born infant without significant past medical history. She had received her regular well child care at 63 days of life and received all of her vaccinations including rotavirus vaccine.

The pertinent physical exam showed an interactive infant without distress. Her weight was increasing at 26 grams/day since her well child care visit. Her examination was normal. The fresh stool in the clinic appeared consistent with the mother’s description and looked normal to the pediatrician.

The diagnosis of a healthy infant with normal stools but exposure to a relative with diarrhea was made. The mother was quite concerned about the possibility of an infectious diarrhea transmitted from the grandmother, therefore a stool enteric panel was run. The laboratory evaluation was negative for any other infectious process except was positive for rotavirus. The pediatrician felt this was due to shedding of the rotavirus vaccine and not a cause of diarrhea. The parent was informed of the results and continued to monitor the infant at home.

Discussion
Vaccination has reduced infectious disease morbidity and mortality since its introduction. Vaccines can be given intramuscularly, subcutaneously or orally. Oral virus vaccines currently used in the US include rotavirus, cholera, typhoid and adenovirus. Adenovirus vaccine is used in military personnel. As these are attenuated viruses there is concern for household contacts who are immunocompromised who may inadvertently be exposed to the virus through fecal shedding. Additionally, there is a concern that the attenuated virus may mutate and revert back to its wild-form and potentially cause disease.

Injectable polio vaccine is used in the U.S. and oral polio vaccine (OPV) is not used. Wild type polio type 2 was officially eradicated in 2015, and type 3 has not been detected globally since 2012, leaving type 1 as the most common circulating type.

The World Health Organization states in May 2012 that “…at least one dose of inactivated poliomyelitis vaccine (IPV) should be introduced into all routine immunization programmes globally, and trivalent oral polio vaccines (tOPV) will be replaced with bivalent (bOPV) in all OPV-using countries. The global “OPV Switch” was successfully conducted worldwide in April 2016 – setting the stage for the eventual withdrawal of all OPV.”

Learning Point
In an Australian birth cohort study in 2017, rotavirus was detected in 9.6% of stool swabs. “Proportions of infants shedding RotaTeq after first, second and third vaccine doses were 87.0%, 57.4% and 47.3%, respectively,…” with median durations of 3 (range 1-8), 1.5 (1-3) and 1 (1-2) weeks respectively. Other studies cite similar time frames. Per the American Academy of Pediatrics RedBook® “Infants living in households with immunocompromised people can be immunized. Highly immunocompromised patients should avoid handling diapers of infants who have been vaccinated with rotavirus vaccine for 4 weeks after vaccination.”

Cholera vaccine (VaxChora®) is known for shedding for at least the first 7 days but length of shedding has not been determined.

In a 2005 study of oral typhoid vaccine, fecal shedding was not detected at 7 or greater days after vaccination.
The American Academy of Pediatrics RedBook® do not currently have recommendations regarding infants living in households with immunocompromised people for cholera and typhoid vaccine.

For wild polio the “[v]irus persists in the throat for approximately 1 to 2 weeks after onset of illness and is excreted in feces for 3 to 6 weeks. Patients potentially are contagious as long as fecal excretion persists. In recipients of OPV, virus also persists in the throat for 1 to 2 weeks and is excreted in feces for several weeks, although in rare cases excretion for more than 2 months can occur. ” “IPV is recommended for these [infants and others who have immunocompromised household contacts], and OPV should not be used. If OPV inadvertently is introduced into a household of an immunocompromised or HIV-infected person, close contact between the patient and the OPV recipient should be minimized for approximately 4 to 6 weeks after immunization.”

Questions for Further Discussion
1. How common is rotavirus infection and what problems does it cause?

2. What vaccine properties cause them to be given intramuscularly, subcutaneously or orally?

3. What other diseases are vaccines being developed for?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for these topics: Immunization and Rotavirus Infections.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Kirkpatrick BD, Tenney KM, Larsson CJ, O’Neill JP, Ventrone C, Bentley M, Upton A, Hindle Z, Fidler C, Kutzko D, Holdridge R, Lapointe C, Hamlet S, Chatfield SN.
The novel oral typhoid vaccine M01ZH09 is well tolerated and highly immunogenic in 2 vaccine presentations.
J Infect Dis. 2005 Aug 1;192(3):360-6.

Anderson EJ. Rotavirus vaccines: viral shedding and risk of transmission. Lancet Infect Dis. 2008 Oct;8(10):642-9.

Brenneman K, McDonald C, Kelly-Aehle SM, Roland KL, Curtiss R 3rd.
Use of RapidChek® SELECTTM Salmonella to detect shedding of live attenuated Salmonella enterica serovar Typhi vaccine strains. J Microbiol Methods. 2012 May;89(2):137-47.

Taniuchi M, Begum S Uddin MJ, Platts-Mills JA, Liu J, Kirkpatrick BD, et.al.
Following oral vaccination as measured by quantitative reverse transcription-PCR versus culture. J Clin Microbiol. 2015 Jan;53(1):206-11.

Vaxchora (Cholera vaccine, live, oral) prescribing information Redwood City, California: PaxFax, inc.: 2016.
Available from the Internet at: https://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm506235.pdf

Mosley JF 2nd, Smith LL, Brantley P, Locke D, Como M.Vaxchora: The First FDA-Approved Cholera Vaccination in the United States. P T. 2017 Oct;42(10):638-640.

Famulare M, Selinger C, McCarthy KA, Eckhoff PA, Chabot-Couture G.
Assessing the stability of polio eradication after the withdrawal of oral polio vaccine. PLoS Biol. 2018 Apr 27;16(4):e2002468.

American Academy of Pediatrics. Cholera, In Kimberlin, DW, Brady, MT, Jackson, M, and Long SS. eds. Red Book: 2018-21 Report of the Committee on Infectious Diseases. 30th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2018.
Available from the Internet at https://redbook.solutions.aap.org/chapter.aspx?sectionid=189640178&bookid=2205 (cited 1/11/19).

American Academy of Pediatrics. Polio, In Kimberlin, DW, Brady, MT, Jackson, M, and Long SS. eds. Red Book: 2018-21 Report of the Committee on Infectious Diseases. 30th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2018.
Available from the Internet at https://redbook.solutions.aap.org/chapter.aspx?sectionid=88187218&bookid=1484 (cited 1/11/19).

American Academy of Pediatrics. Rotavirus, In Kimberlin, DW, Brady, MT, Jackson, M, and Long SS. eds. Red Book: 2018-21 Report of the Committee on Infectious Diseases. 30th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2018.
Available from the Internet at https://redbook.solutions.aap.org/chapter.aspx?sectionid=189640175&bookid=2205 (cited 1/11/19).

American Academy of Pediatrics. Salmonella, In Kimberlin, DW, Brady, MT, Jackson, M,and Long SS. eds. Red Book: 2018-21 Report of the Committee on Infectious Diseases. 30th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2018.
Available from the Internet at https://redbook.solutions.aap.org/chapter.aspx?sectionid=189640178&bookid=2205 (cited 1/11/19).

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

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How Common Is Unintentional Cannabis Ingestion?

Patient Presentation
A full-term female was born to a 26 year old G4P4 female by vaginal delivery without complications. She was given routine care and was doing well at 24 hours after delivery. The social history revealed that the mother was known to smoke marijuana frequently, and had a positive urine drug testing for marijuana during this pregnancy. A male sibling had also been admitted for an unintentional cannabis exposure after the toddler had ingested his mother’s unfinished marijuana cigarette. The father of the baby smoked cigarettes and smokeless tobacco, and had some beers on the weekend. He denied any substance abuse. Both parents were employed and all of the children were living with them.

The pertinent physical exam showed a healthy female with normal vital signs. She had a weight and head circumference at the 10% and length of 50%. She had no physical anomalies noted and had a normal exam. The diagnosis of a healthy female with prenatal cannabis exposure was made. A urine toxicology screening was sent on the infant and eventually was positive for cannabis only. The state’s Department of Human Services was contacted and continued to follow the family over the next year. The mother had entered a substance abuse treatment program but was inconsistent in going to the program.

The patient’s clinical course showed her to continue to grow appropriately but she still was at the 10-15% for head circumference and weight over the next year. She also had normal development. The family was lost to followup after the 12 month appointment.

Discussion
“[Cannabis] is a genus of flowering plant with three main varieties: sativa, indica and ruderalis.” It has been used for hundreds of years for hemp or fiber and also for psychoactive and medicinal effects. The active compounds are collectively called cannabinoids, of which delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most abundant. The floral buds or calyxes of the plant have the most cannabinoids, but other parts of the plant are also used such as leaves. Hash oil, hashish (or resin) and marijuana (dried leaves) are the common products from strongest to least strongest products. (Hash oil is not the same as Hemp oil. Hemp oil is often sold over the counter and contains little cannabinoids). Cannabis is smoked (like or with tobacco) or vaporized (like an e-cigarette) or ingested in drinks or food. Cannabis like many psychoactive drugs is lipophilic which allows it to easily cross the blood-brain or placental barriers and to remain within the fat tissue and therefore can be concentrated and its effects can last up to weeks. THC half-life is several days to a week. Cannabis’s “[a]cute effects include … Relaxation, euphoria, heightened perception, sociability, sensation of time slowing, increased appetite and decrease pain, and on the other hand paranoia, anxiety, irritability, impaired short-term memory, poor attention and judgment, and poor coordination and balance. Physiologic effects include tachycardia, hypertension, dry mouth and throat, and conjunctival injection.”

Cannabis is used by about 3.9% of the world’s population. For drug users, it is the most commonly abused drug. Up to ~40% of adults have used cannabis at some time in their lifetime. It is commonly used in pregnant and lactating women (~2.5 – 5.0% depending on the population). Marijuana use is on the increase for teens with an overall use of ~7% and ~23% of 12th graders in the U.S. have used it in the past month (Data from 2013).

Cannabis research has been difficult because different definitions (such as defining what is regular or significant use) or confounding factors such as concurrent substance abuse (e.g. tobacco, alcohol, other), poor nutrition, lifestyle, and parenting effects. Infants, whose mother’s used cannabis, have an increased associated with low birth weight and growth restriction, smaller head growth (that continues through adolescence), cognition, visual-perceptual skills, verbal-reasoning skills, language skills, specific learning problems, attention and depression. Regular cannabis use by adolescents has been linked to a decline in intelligence quotient through age 38 that is not reversed with discontinuation of cannabis use. Adolescent cannabis use has also been linked to depression (but not suicide) and possibly anxiety disorders. Cannabis use during times of critical brain development such as fetal and young children and adolescence, increases the risk of neurological impairment.

Medical use has been proposed and mainly studied in adult populations. Potential indications include cancer-related nausea, appetite enhancement, neurogenic pain, glaucoma and epilepsy. In pediatrics some of the most common use is for seizures, but also chronic pain and muscle spasms. CBD is the more common form of cannabis used for seizures. Currently available data for developmental or behavioral conditions such as ADHD, oppositional defiant disorder, or autism spectrum disorder are case-studies or small series. Research agendas have been proposed to try to answer many of the important but unclear or not available research voids.

Learning Point
Unintentional ingestion by young children is increasing as cannabis is available legally or illegally within their environments. When comparing data from states where cannabis is not legal or legal, the numbers of phone calls to poison control centers from 2005-2011, showed an increase of 1.5% in non-legal states, but a 38.5% increase in legal states. In legal states, there was also an increase in the number of moderate or major effects and hospital admissions (overall admission = 16%). There was also a small number but increased admissions to intensive care settings.

Young children are more likely to orally ingest cannabis as resin, food (cookies) or unfinished marijuana cigarettes (joints). They can also be exposed through candies and beverages or other food products which are often marketed to look like non-cannabis food products. Hash resin itself looks similar to a chocolate candy bar. There is little data about passive exposure to cannabis smoke exposure but cannabis smoke has been shown to have similar components to nicotine/tobacco smoke including potential carcinogens. Cannabis products such as hash oil or resin are being used by some though vaporization (similar to e-cigarettes). The most common symptoms of unintentional ingestion were lethargy, followed by tachycardia, mydriasis and hypotonia.
“The unintentional ingestion of cannabis by children is a serious public health concern and is well-documented in numerous retrospective studies, case-series, and case reports. Clinicians should consider cannabis toxicity in any child with a sudden onset of lethargy or ataxia. Hypotonia, mydriasis, tachycardia, and hyperventilation represent other common clinical findings of cannabis toxicity. As cannabis legalization, availability, and potency increases so does the possibility for the rising incidence of unintentional pediatric cannabis intoxication, which frequently requires hospitalizations, and, in some cases, admission to the PICU for airway support.”

Questions for Further Discussion
1. What types of body fluids or tissues can be tested for cannabis?
2. What is the legal status of cannabis in your state or country? If legal in some form, how is medical cannabis prescribed and distributed?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for these topics: Marijuana and Pregnancy and Substance Abuse.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Jaques SC, Kingsbury A, Henshcke P, Chomchai C, Clews S, Falconer J, Abdel-Latif ME, Feller JM, Oei JL. Cannabis, the pregnant woman and her child: weeding out the myths. J Perinatol. 2014 Jun;34(6):417-24.

Hadland SE, Knight JR, Harris SK. Medical marijuana: review of the science and implications for developmental-behavioral pediatric practice. J Dev Behav Pediatr. 2015 Feb-Mar;36(2):115-23.

Richards JR, Smith NE, Moulin AK. Unintentional Cannabis Ingestion in Children: A Systematic Review. J Pediatr. 2017 Nov;190:142-152.

Wang GS. Pediatric Concerns Due to Expanded Cannabis Use: Unintended Consequences of Legalization. J Med Toxicol. 2017 Mar;13(1):99-105.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

What Are the Types of Tracheoesophageal Fistulas?

Patient Presentation
A full-term male was born by vaginal delivery to a 24 year G1P1 female. In the delivery room, he had some difficulty breathing and was taken to the transition bed for monitoring. The nurse noted that he seemed to have more secretions and needed frequent suctioning. She tried to pass an NG tube to suction his stomach but was not able to pass it more than a few centimeters. He was taken to the neonatal intensive care unit, where his respiratory distress seemed to improve, but when he attempted to eat, he had a poor suck and had regurgitation. His tachypnea resumed. Again a nasogastric tube was tried, but could not be passed and on radiograph was found coiled in the proximal esophagus. The diagnosis of esophageal atresia and tracheoesophageal fistula was made. He was taken to the operating room and found to have proximal blind pouch esophageal atresia with a distal tracheoesophageal fistula. He was extubated on day 3 of life and was discharged on day 15 after surgical recovery and being able to take full oral feedings.

Discussion
Respiratory problems in infants can caused by many things including any type of obstruction from the nose to lung. Neonates and infants are particularly susceptible to changes in the size of the airway because of the physics of airflow resistance. Important reminders about infant airways:

  • Resistance = 1/radius4 (Poiseuille’s equation) therefore even a 1 mm decrease in the airway circumferences increases the airflow resistance x16.
  • Increased airflow causes less pressure along the walls, which can lead to collapse of the walls (Bernoulli’s and Venturi effects).
  • Neonates have smaller lungs relative to the rest of their body therefore they have less pulmonary reserve.
  • Neonates have higher oxygen consumption rates (about 50% more) than older children and adults.
  • Neonates are preferential nose breathers.
  • Neonates have immature regulation of vital functions and when stressed may do the opposite of what is expected. For example, they may become apneic with respiratory distress instead of increasing their respiratory rate.

Therefore anything that changes the airflow dynamics of the infant airway can cause dramatic effects for a neonate. Health care personnel need to be aware of subtle changes and may need to respond quickly to the infant’s respiratory status, even while trying to determine the cause of the problem.

Learning Point
Esophageal atresia (EA) with tracheoesophageal fistula are anomalies in the continuity of the esophagus with or without tracheal communication.
EA/TEF occurs in about 2500-3000 live births with most being a sporadic/non-syndromic. Familial or syndromic cases are about 1% with examples being CHARGE, VATER or VACTERL associations. To learn more about associations click here.

Presentations can vary depending on the particular type of EA/TEF. Prenatally, polyhydramnios, small or absent stomach bubble on prenatal ultrasound may indicate a EA/TEF. At birth, respiratory distress or cyanosis can occur. At birth or within a short time, increased salivation, regurgitation, coughing or choking on feeding may indicate a problem. Older children may present with recurrent coughing, wheezing, regurgitation or frequent pulmonary infections.

Chest/abdominal radiographs may show an air filled abdomen, or failed placement of NG tube (i.e. curled up in esophagus). H-type fistulas are difficult to detect by many means including upper gastrointestinal radiographic studies and even endoscopy.

The Gross Classification of EA/TEF includes:

  • A – Isolated EA without TEF, 7-8.5%
  • B – EA with proximal TEF, 1 to 2%
  • C – “Blind pouch”, proximal EA with a distal TEF attached posteriorly to trachea, 85 – 86%
  • D – “Double fistula”, EA with proximal and distal TEF, ~1%
  • E – “H-type fistula”, TEF present between intact esophagus and trachea, 4%

The Vogt classification is similar but also includes absent esophagus. Concurrent anomalies occur in about 50% of patients including “…cardiovacular (29%), anorectal (14%), genitourinary (14%), gastrointestinal (13%), vertebral/skeletal (10%), and respiratory (6%) may be present.” Tracheomalacia is not considered a concurrent anomaly by most people, but part of the EA/TEF process. It occurs in about 75% of patients.

Surgery includes ligation of the TEF and anastomosis of the EA. This has been traditionally done by thoracotomy but is being done more often recently by thoracoscopy. Patients usually do well with only an ~2% mortality rate usually because of concurrent anomalies. Short term surgical complications include anastomatic leaks, esophageal stenosis or web, recurrent fistula, vocal fold paralysis, dysphagia, eating problems, gastroesophageal reflux disease and pulmonary infections. Longer term followup shows problems with GERD and pulmonary problems including wheezing or infections. Generally development is normal but children may have communication problems. There are few studies of adults who had EA/TEF as a child so data is sparse but shows GERD and pulmonary problems.

Questions for Further Discussion
1. What are the components of CHARGE association?
2. List other types of tracheal disorders?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for these topics: Esophagus Disorders and Tracheal Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Roberts K, Karpelowsky J, Fitzgerald DA, Soundappan SS. Outcomes of oesophageal atresia and tracheo-oesophageal fistula repair. J Paediatr Child Health. 2016 Jul;52(7):694-8.

Javia L, Harris MA, Fuller S. Rings, slings, and other tracheal disorders in the neonate. Semin Fetal Neonatal Med. 2016 Aug;21(4):277-84.

Vijayasekaran S, Lioy J, Maschhoff K. Airway disorders of the fetus and neonate: An overview. Semin Fetal Neonatal Med. 2016 Aug;21(4):220-9.

van der Zee DC, Tytgat SHA, van Herwaarden MYA. Esophageal atresia and tracheo-esophageal fistula. Semin Pediatr Surg. 2017 Apr;26(2):67-71.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa