Can I Give Cholera Vaccine?

Patient Presentation
A 17-year-old male came to clinic for travel immunizations before a medical mission to Haiti for 2 weeks. His father was a health care provider and had traveled to Haiti on two previous trips, but this trip was to spend more time in more rural locations. His father had been to the travel clinic and had received cholera vaccine along with malaria prophylaxis. He was current with typhoid vaccine. The pertinent physical exam showed a healthy teenager with normal vital signs and growth parameters in the 75-95%. His examination was normal.

The diagnosis of a healthy male was made. The pediatrician reviewed the Centers for Disease Control website for current immunization recommendations for Haiti. The teenager was current with his standard vaccinations and received typhoid vaccine and malaria prophylaxis along with counseling regarding using insect repellent, safe water and hygiene practices. “Unfortunately you just turned 17, and the vaccine in the United States is only for those over 18 years, so I can’t give it to you. It’s really, really important that you use safe water and wash your hands well, ALL THE TIME,” the pediatrician emphasized. The father said that he had been making his son practice at home using bottled water for drinking, toothbrushing and preparing meals. “It’s a lot of work to fill up the bottles from the faucet and practice, but I don’t want to get sick so I guess its okay,” the teen obliged.

Discussion
Cholera is caused by more than 200 serogroups of Vibrio cholerae, a Gram-negative rod that is waterborne. Only two (serogroup O1 which causes about 99% of the cases, and O139) cause disease. There are biotypes of each of these serotypes. The only known hosts are humans. The organism colonizes the epithelial lining of the gut. Cholera toxin is produced by some species and if produced binds to specific receptors on host cells, activating a series of steps which cases massive loss of sodium, potassium, chloride, hydrogen carbonate, and fluids in vomitus and feces. A review of causes of diarrhea can be found here.

More than 1 billion people are at risk for cholera in endemic countries with an estimated 2.86 million cases and ~95,000 deaths annually Cholera is endemic in sub-Saharan Africa and Asia but has areas that have become epidemic such as Haiti and Yemen in the past few years. Studies in Africa have an incidence of < 0.3/10,000 which increased to 20/10,000 during epidemics. About half of the cases and deaths are in children < 5 years of age. For travelers from non-endemic countries cholera is rare with a risk of 0.01-0.001% per month of stay in a developing country. Cholera is rare in the United States with < 25 cases/year reported with most occurring among travelers to epidemic or endemic cholera.

Cholera is spread by direct fecal-oral and contaminated water or food routes thus the risk of cholera increases in areas where crowding, lack of access to clean water, sanitation and health care are issues. Incubation period is < 24 hours to 5 days. Only 1-25% of those exposed actually develop disease. Of those that are symptomatic, 10-20% experience severe disease. Symptomatic patients produce watery diarrhea sometimes referred to as "rice water stools." Emesis can also occur. Symptoms last 1 to a few days. Patients can have profuse fluid loss of up to 0.5 – 1.0 liters/hour and obviously severe dehydration is a major cause of morbidity and mortality if not promptly and aggressively treated. Healthy persons have been known to die within 24 hours of symptom onset because of the complications of dehydration.

Risk factors for cholera include number of bacteria ingested, lack of immunity from prior disease or vaccination, lack of passive immunity for newborn infants because of lack of breastfeeding, pregnancy, immunocompromised state (especially HIV), malnourishment, blood group O, and decreased ability to make gastric acid which neutralizes the bacteria. High concentrations of the bacteria is found in feces, and often vomitus also. There is some data suggesting “…that passage through a human host transiently increases the infective potential of V. cholerae by creating a hyperinfectious state that is maintained soon after shedding, and which may contribute to the epidemic spread of the disease.”

The diagnosis standard is by culture, but polymerase chain reaction testing and other rapid diagnostic testing is also available. Treatment is by rapid and aggressive administration of fluid and electrolytes. In patients with mild to moderate dehydration, oral rehydration with low osmolarity oral rehydration solution (ORS) is standard. The lower osmolarity compared to standard ORS decreases emesis. For severe dehydration, intravenous fluid administration with correction of electrolytes is imperative. Antibiotics are given to hospitalized patients during epidemics which decreases the symptom duration, stool volume, and length of time the active pathogen is excreted which reduces transmission and hospital length of stay. Doxycycline is usually the first choice, but ciprofloxacin or azithromycin are used in doxycycline-resistant areas. Unfortunately drug-resistance is common.

Although both children and adults are able to mount antibody responses to both the organism and the toxin, they are not reliably predictive of protection against cholera.

Learning Point
Cholera vaccines are available for use in endemic and epidemic areas, and for travelers.

  • Dukoral® is a whole-cell, killed, monovalent vaccine again serotype O1
    • Has a cholera toxin subunit which also has some cross-reactivity with enterotoxigenic Escherichia coli and therefore it offers some protection for this entity also
    • Given orally
      • 3 doses for children given 1-6 weeks apart for ages 2-5 years
      • 2 doses are given 1-6 weeks apart for ages 6 years and up
    • Protection is 6 months for children 2-5 years, and 2 years for those 6 years and older
    • For revaccination
      • For children 2-5 years, 1 dose can be used if given within 6 months of primary immunization, otherwise re-start primary vaccination
      • For 6 years and up, 1 dose can be used if given within 2 years of primary immunization, otherwise re-start primary vaccination
    • Licensed in countries worldwide, primarily for travelers to endemic countries but has been used for epidemics
  • Shanchol™, Euvichol®, and mORCVA™ are modified whole-cell, killed, bivalent vaccine against serotypes O1 and O139
    • These 3 vaccines are based on the same strains but are available in different areas of the world.
    • Does not have cholera toxin subunit therefore is no cross-reactivity with enterotoxigenic Escerichia coli
    • Given orally
      • 2 doses given 14 days apart for ages 1 year and older
    • Protection is up to 5 years
    • Licensed in countries worldwide, for travelers and also for epidemics
  • Vaxchora® is a live-attenuated single-dose oral vaccine.
    • It is the only cholera vaccine available in the United States and is given as a single oral dose to people ages 18-64 years for those traveling to cholera-affected areas.
    • Its protection is at least 3 months according to the Centers for Disease Control, but others studies have shown efficacy for 6 months.

The World Health Organization recommends during humanitarian emergencies where there is a risk of cholera but no current outbreak that oral cholera vaccine be considered as an additional measure for prevention. International workers and travelers should also use safe hygiene practices. Emergency/relief workers who would be likely to encounter patients with cholera or exposed to contaminated food and water should be vaccinated. “Vaccination is not generally recommended for long-term or short-term travelers to cholera-affected countries,….”

Other vaccines are currently being developed.

Questions for Further Discussion
1. What are good “hygiene” practices for places with risks for fecal-oral transmission of infections?
2. What are good malaria prevention practices?

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, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Cholera and Traveler’s Health.

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.

Tran NT, Taylor R, Antierens A, Staderini N. Cholera in Pregnancy: A Systematic Review and Meta-Analysis of Fetal, Neonatal, and Maternal Mortality. PLoS One. 2015 Jul 15;10(7):e0132920.

Das JK, Ali A, Salam RA, Bhutta ZA. Antibiotics for the treatment of Cholera, Shigella and Cryptosporidium in children. BMC Public Health. 2013;13 Suppl 3:S10.

Cabrera A, Lepage JE, Sullivan KM, Seed SM. Vaxchora: A Single-Dose Oral Cholera Vaccine. Ann Pharmacother. 2017 Jul;51(7):584-589.

Wong KK, Burdette E, Mahon BE, Mintz ED, Ryan ET, Reingold AL. Recommendations of the Advisory Committee on Immunization Practices for Use of Cholera Vaccine. MMWR Morb Mortal Wkly Rep. 2017 May 12;66(18):482-485.

Cholera vaccines: WHO position paper – August 2017. Wkly Epidemiol Rec. 2017 Aug 25;92(34):477-98.

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

Can Fish Oil Help Reading?

Patient Presentation
A 10-year-old female came to clinic for her health maintenance examination. She was doing well physically and had many friends socially. She was having problems at school in reading where she was getting additional help and was making some progress. However she still remained behind her classmates. Her teachers and parents did not describe problems in other areas including executive function or attention. The family history revealed that her father had some reading problems as a child. The pertinent physical exam showed a smiley female with growth parameters in the 50-75%. Her examination was normal.

The diagnosis of a healthy female with a reading disability was made. The mother asked about supplementing with fish oil as her friend used it for her child who had some developmental problems. The pediatrician said that she didn’t know a lot about using it, but a quick review of the National Institutes of Health Complimentary and Alternative Medicine website showed that while there was not data to support its use for learning problems, fish oils had few side effects. “I guess that you could use them, but you could also use the money for something else too,” she said. “I do recommend that you continue to work with the teachers and follow her closely. She may need more help than she is getting now but you will only know that by working with the teachers,” she counseled.

Discussion
Fats and fatty acids are essential for good human health.

Saturated fats have hydrogen pairs linked to each carbon on the carbon backbone. They are solid or semi-solid at room temperature. Common examples are butter, lard, or hardened vegetable shortening. They are linked to higher cholesterol and triglycerides and only a small amount of them are recommended to be consumed in the diet.

Unsaturated fats have one or more hydrogen atoms missing from the carbon backbone. They are liquid at room temperature.

  • Monounsaturated fatty acids have one hydrogen pair that is missing from the carbon backbone. They are liquid at room temperature but start to become solid when placed into the refrigerator. Common examples are Canola oil, olive oil, peanut oil and avocados.
    They lower total and LDL cholesterol and increase HDL cholesterol.

  • Polyunsaturated fatty acids (PUFAs) have two or more hydrogen pairs that are missing from the carbon backbone. They are liquid at room temperature and when cooled. Common examples are corn oil, soybean oil, and the seeds and oil made from safflower, sesame, and sunflower seeds.
    They lower total and LDL cholesterol but also lower HDL production.

  • Omega-3 fatty acids are a type of polyunsaturated fats derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). They are commonly found in fatty fish such as mackerel, albacore tuna, sardines, salmon, herring, anchovies, sardines and lake trout. They can also be found in Canola oil, soybean oil, flaxseed oil, and walnuts. They are also a component of human breast milk.
    Omega-3 fatty acids lower total cholesterol and triglycerides.

Learning Point
Omega-3s have been shown to decrease cardiovascular disease including heart attack, arrhythmias, stroke and sudden cardiac death. Omega-3s help to regulate the immune system and they have been shown to “…decrease inflammation and be useful in the treatment of rheumatoid arthritis, [inflammatory bowel disease], and psoriasis.” Some studies support a benefit also in Alzheimer disease and depression. Omega-3s also help fetal brain development and have been added to infant formulas since 2002 to be more like breastmilk.

Current data does not support Omega-3 supplementation for improved cognition, inhibition, attention, memory, reading, reaction times, and autism spectrum disorder. Even in infant formula trials, the end-point that is measured appears to affect the outcome, and the authors concluded that “[a]vailable data are currently inadequate to conclude that [Omega-3]supplementation has a clinically meaningful beneficial effect upon neurological development.”

Fatty fish also have higher levels of mercury and toxins (especially polychorinated biphenyls and dioxin) and therefore the pros and cons of fatty fish must be balanced, and two servings of fatty fish (3-4 ounces/serving) are recommended weekly that is broiled or baked. Frying is not recommended. High levels of mercury are found in shark, swordfish, king mackerel, and tile fish (also called golden snapper or golden bass) but low levels are found in anchovies, catfish, sardines, salmon, pollock, clams, oysters and shrimp. The fish listed as having high levels of mercury are not recommended to be consumed during pregnancy, breastfeeding and for young children. Supplements of fish oil or Omega-3s have not shown to have the same benefit for cardiac disease as eating the fish itself.

Questions for Further Discussion
1. What approach to complimentary and alternative medicine to you take when discussing it with patients?
2. What sources of information for complimentary and alternative medicine do you recommend to patients?

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, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Dietary Supplements and Learning 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.

University of Illinois Extension. What are Polyunsaturated and Monounsaturated Fats?
Available from the Internet at http://extension.illinois.edu/diabetes2/subsection.cfm?SubSectionID=46 (rev. 6/2014, cited 9/25/17).

National Center for Complimentary and Alternative Medicine. Omega-3 Supplements: In Depth.
Available from the Internet at https://nccih.nih.gov/health/omega3/introduction.htm (rev. 8/2015, cited 9/25/17).

Cooper RE, Tye C, Kuntsi J, Vassos E, Asherson P. Omega-3 polyunsaturated fatty acid supplementation and cognition: A systematic review and meta-analysis. J Psychopharmacol. 2015 Jul;29(7):753-63.

Sun H, Como PG, Downey LC, Murphy D, Ariagno RL, Rodriguez W. Infant formula and neurocognitive outcomes: impact of study end-point selection. J Perinatol. 2015 Oct;35(10):867-74.

Parian AM, Mullin GE. Fish Consumption and Health: The Yin and Yang. Nutr Clin Pract. 2016 Aug;31(4):562-5.

Gould JF, Treyvaud K, Yelland LN, Anderson PJ, Smithers LG, McPhee AJ, Makrides M. Seven-Year Follow-up of Children Born to Women in a Randomized Trial of Prenatal DHA Supplementation. JAMA. 2017 Mar 21;317(11):1173-1175.

Horvath A, Lukasik J, Szajewska H. Omega-3 Fatty Acid Supplementation Does Not Affect Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis. J Nutr. 2017 Mar;147(3):367-376.

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

How Long Do Late Preterm Infants Need Supplemental Feedings?

Patient Presentation
A 19 day old, former 35 1/7 week late preterm male infant came to clinic for his first appointment after he was discharged from the neonatal intensive care unit. He was breastfeeding every 2-2.5 hours for 10 minutes and then parents would syringe feed him breastmilk that was fortified to 24 kcal/ounce with premature infant powdered formula. He would take about 10 ml after most feeds. His weight gain had been averaging 15-20 grams/day before discharge, and since he had been home for the last 4 days it had been 10-15 grams/day . His mother noted that he still seemed quite sleepy but would appropriately arouse, eat and then fall back to sleep. “Since we’ve been home though, its probably closer to every 2.5 hours feeding than the 2 hours we were doing in the hospital,” she said. The past medical history showed a neonatal intensive care course where he received antibiotics for 48 hours as his mother was Group B streptococcus positive and had not been adequately treated with antibiotics before delivery. His laboratory values and cultures were negative and his antibiotics were then stopped. He had mild respiratory distress initially that was treated by nasal canula for 3 days. He also had poor feeding so he received parenteral nutrition for 6 days, transitioned to gavage feedings and then to full oral feeds.

The pertinent physical exam showed a small infant with normal vital signs. His birth weight had been 2.230 kg (10-50% on Fenton premature infant growth chart) and now was 2.544 kg (10%). His length was 48 cm (10%) and his head circumference was 34 cm (50%). He had an open, flat fontanelle without overriding sutures. He had some subcutaneous fat but was still somewhat thin. His examination was otherwise unremarkable. The diagnosis of a late preterm infant who was now feeding and growing was made. The pediatrician recommended that the family continue the current feeding regimen but to also try to feed the infant closer to every 2 hours. “We don’t want to tire him out, but if he eats closer to every 2 hours then he’ll get another 1-2 feedings a day and that is huge for him and his growth. I also would not limit the amount he takes by syringe. If he seems hungier you can give him more, but I would try to give him at least 10 ml,” he recommended.

The patient’s clinical course the following week showed him to be gaining 20 g/day. “We’ve been feeding him closer to every 2 hours, plus he seems to be eating better at the breast. He’s only taking about 5 mls after feedings,” described his mother. “He’s obviously growing and doing better. I’m glad to hear that he is breastfeeding better. He’s still not full-term yet so I’d continue to offer the fortified supplement,” said the pediatrician. Over the next 2 weeks, the infant started to breastfeed more vigorously and stopped taking the supplements. At 41 weeks adjusted age, he was 3.432 kg (10-50%), and was not taking any supplementation.

Discussion
Premature infants have many problems to overcome because they just aren’t ready to live outside the uterine environment.
Late premature infants are defined as birth between 34 0/7 weeks and 36 6/7 weeks gestation. In the U.S. this gestational age accounts for ~70% of all preterm births or ~300,000 births/year. Late preterm infants can have delayed oral feeding skills and failure to thrive along with increased hospital readmissions. Breastfeeding can be difficult as infants can have poor coordination and poor tone, along with decreased lactation in the mother.

Learning Point
Weight gain lags behind intrauterine weight gain in premature infants including late preterm infants. The intrauterine growth is ~15 g/day at this age and in one study only 2% of preterm infants achieved this weight gain. Late preterm infants have increased energy, protein, calcium and phosphorous needs as this is the time that the fetus would be storing fat and minerals. It is also a time when brain growth and volume are markedly increased. Late preterm infants need additional nutritional supplementation. Therefore it is recommended that late preterm infants be breastfed with fortified human milk until at least 40 weeks postconceptional age. Human milk fortifier or special preterm discharge formula are recommended for use as the supplements as they contain additional calories, protein and minerals compared to standard infant formula. Preterm infants that are born earlier and weigh less, not surprisingly need supplemental nutrition for longer. For infants 25 grams/day) and reaches term weight (~3.25 kg). For formula fed infants, fortified formula with a premature infant formula at 22 kcal/ounce should be offered until the infant is 40 weeks postconceptional age and term weight. Then the infant can be transitioned to term formula at 20 kcal/ounce.

Questions for Further Discussion
1. What are indications for enteral or parenteral nutrition in preterm infants?
2. By what age should preterm infants be “caught-up” and following term infant growth patterns?
3. What nutritional supplementation do low birth weight or extremely low birth weight infants need?
4. What are some advantages of human donor breastmilk? They can be reviewed here

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, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Premature Babies and Child Nutrition.

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.

Carlson SK, Segar JL. Nutritional Needs of the Late Preterm Infant.
The Iowa Perinatal Letter. 2014;32(2).

Gianni ML, Roggero P, Piemontese P, et.al. Is nutritional support needed in late preterm infants? BMC Pediatr. 2015 Nov 23;15:194.

Raaijmakers A, Allegaert K. Catch-Up Growth in Former Preterm Neonates: No Time to Waste. Nutrients. 2016 Dec 17;8(12). pii: E817.

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