We deal with vaccinations. Part 21. Rotavirus

2024 Author: Seth Attwood | [email protected]. Last modified: 2023-12-16 15:55

1. Before the advent of the vaccine, few people had heard of rotavirus infection, despite the fact that almost all children were sick with it.

2. CDC Pinkbook

The rotavirus was discovered in 1973 and was named that because it looks like a wheel. The virus is the most common causative agent of gastroenteritis in infants and children. It is transmitted by the fecal-oral route.

The first infection after 3 months of age is usually the most severe. It can be asymptomatic, it can cause mild diarrhea, or it can cause severe diarrhea with high fever and vomiting. Symptoms usually resolve in 3-7 days. Similar symptoms can be caused not only by rotavirus, but also by other pathogens, therefore laboratory analysis is necessary to confirm.

In temperate climates, the disease is more common in the fall and winter.

There are currently two oral rotavirus vaccines available: Rotatec and Rotarix. Rotatek is given 3 doses (at 2, 4 and 6 months) and Rotarix two doses (at 2 and 4 months). The first dose should not be given after 14 weeks, and the last dose should not be given after 8 months.

Vaccines are 74-98% effective against the serotypes they contain. How long immunity lasts is unknown.

Since the efficacy and safety of more than one dose has not been studied, it is not recommended to give your baby another dose of the vaccine if he spits it out or spits it up.

In clinical trials, diarrhea and vomiting were more often recorded in the vaccinated Rotatek in the first week after vaccination than in the placebo group. Within 42 days after vaccination, the vaccinated were more likely to have diarrhea, vomiting, otitis media, nasopharyngitis, and bronchospasm.

Vaccinated Rotarix were more likely to have cough and runny nose within 7 days, and irritability and flatulence were more likely to appear within a month after vaccination, compared with the "placebo" group.

3. Rotavirus infection in infants as protection against subsequent infections. (Velázquez, 1996, N Engl J Med)

The likelihood of diarrhea in primary rotavirus infection is 47%. With subsequent infections, the likelihood of diarrhea is reduced.

Previous rotavirus diarrhea reduces the risk of diarrhea from subsequent infections by 77% and the risk of severe diarrhea by 87%. Two / three diarrhea from rotavirus reduces the risk of subsequent infections by 83% / 92%.

A previous asymptomatic infection reduces the risk of subsequent infections by 38%.

Two previous infections (whether symptomatic or asymptomatic) provide 100% protection against severe diarrhea.

A short period of breastfeeding increases the risk of rotavirus infection.

4. Human immunity to rotavirus. (Molyneaux, 1995, J Med Microbiol)

Re-infection with rotavirus is possible, but it goes away with mild or no symptoms.

In total, there are 7 serotype groups of the virus (A-G). Group A is divided into serotypes G1-G14, P1-P11 and others. People are infected mainly with serotypes G1-G4 in group A, and less often in groups B and C.

In newborns, the infection is usually asymptomatic. Subsequently, they become ill with rotavirus less often and get sick more easily than those who were not infected after birth. Infection in infancy, whether symptomatic or asymptomatic, gives protection for 2 years. After a period of early childhood, symptomatic infection is rare.

Exclusive breastfeeding in the first year of life reduces the risk of infection.

In the 90s, they began to develop vaccines against rotavirus, so the CDC wondered how many children die from it. To do this, they conducted the following studies:

5. Diarrheal deaths in American children. Are they preventable? (Ho, 1988, JAMA)

Deaths from diarrhea (from all causes) account for 2% of all postneonatal deaths. In 1983, 500 children were dying of diarrhea in the United States, of which 50% died in hospital. Mortality from diarrhea drops sharply with age, twice as high among infants 1–3 months of age as compared to 4–6 months of age, and 10 times higher than among 12 months of age.

The risk of dying from diarrhea is 4 times higher among blacks (and in some states 10 times higher) than among whites; 5 times higher among infants whose mothers are under 17; 2 times higher among those whose parents are unmarried; 3 times higher among those whose parents did not finish school.

Deaths from diarrhea are higher in winter than in summer, and rotavirus is thought to be responsible. It is estimated that 70-80 children per year die from rotavirus.

6. Trends of diarrheal disease - associated mortality in US children, 1968 through 1991. (Kilgore, 1995, JAMA)

From 1968 to 1985, deaths from diarrhea in the United States decreased by 75% (among infants - by 79%), and then stabilized. Between 1985 and 1991, 300 people a year died of diarrhea, 240 of them children. The fatality rate of diarrhea among children was 1: 17,000. Since 1985, half of them have died before reaching 1.5 months of age (that is, before the age of vaccination).

Here is a graph of deaths from diarrhea from 1968 to 1991:

Each winter, one can observe peaks in mortality, which disappear in the mid-80s, and only small peaks remain in the group of 4-23 month olds. Since rotavirus is sick almost exclusively in winter, the authors believe that this is the death from rotavirus.

The authors conclude that rotavirus vaccines will have a measurable but small effect on diarrheal mortality.

7. The epidemiology of rotavirus diarrhea in the United States: surveillance and estimates of disease burden. (Glass, 1996, J Infect Dis)

It is estimated that 873,000 people a year die from rotavirus worldwide. But there was no information on the mortality rate of rotavirus in developed countries, and therefore in 1985 the IOM concluded that this vaccine was not a priority for the United States. But they were based on one prospective study, although other studies have found that a third of children hospitalized with diarrhea have rotavirus infection.

Since no child in the United States died with a diagnosis of rotavirus diarrhea, many pediatricians believed that rotavirus was never serious or fatal. However, analysis of mortality data (in previous studies) has provided compelling, albeit circumstantial, evidence that rotavirus does die.

Based on two previous studies, the authors estimate that 55,000 children per year are hospitalized from rotavirus and 20 children die, ie. 1 in 200,000. They believe that these babies have some other medical condition, or that they are premature, for example.

The authors conclude that fewer than 40 children die from rotavirus a year, although they do not explain where they got 40 from if they counted only 20 in the text of the article.

The CDC writes that 20-60 children a year die from rotavirus, but they do not explain where they got 60 children from if their own research has counted only 20.

8. Rotavirus vaccines: viral shedding and risk of transmission. (Anderson, 2008, Lancet Infect Dis)

- The first rotavirus vaccine (Rotashield) was licensed in 1998 and contained 4 strains. It was withdrawn in 1999 because it was associated with intussusception. Intussusception is when a part of the intestine folds on itself like a telescope.

- The public is unwilling to put up with even the smallest risk of serious side effects. Even as low as 1 in 10,000.

- In 1998 the Rotarix vaccine (GSK) was licensed. Contains one strain. The isolated strain from the infected child was attenuated through 33 serial transitions through the kidney cells of African green monkeys. The vaccine strain multiplies well in the human intestine.

- The Rotateq vaccine (Merck) was licensed in 1996. Contains 5 strains. (Our friend Paul Offit holds four patents for this vaccine.)

Unlike other live vaccines, Rotatec is not an attenuated vaccine, but a reassortant vaccine.

The rotavirus genome consists of 11 RNA segments. In vaccine strains of Rotatek, some of the segments have been replaced from human rotavirus to bovine rotavirus. Such vaccines, where some segments of the RNA of the virus are replaced with segments of animal strains of the virus, are called reassortant vaccines. Rotatec is a pentavalent vaccine. The four most common serotypes (G1-G4) are combined with bovine serotype P. The fifth strain consists of bovine serotype G combined with human serotype P. Three vaccine strains are reassortant from one human and ten bovine segments. The other two are reassorted from two human and nine bovine segments. Such a virus does not multiply well in the intestines, therefore Rotatek contains 100 times more viral particles than Rotarix.

The first vaccine (Rotashield) was also reassortant, but it used segments of the monkey virus.

The vaccine contains polysorbate 80 and fetal bovine serum.

In clinical trials of both vaccines, the same vaccine was used as a placebo, but without the virus [1], [2].

- During Rotashield clinical trials, vaccine strains began to be detected in the stool of those who received a placebo one year after the start of the trial, and ceased to be detected after 100 days after the trial, indicating the establishment of a "community reservoir".

- In clinical trials, Rotarix found that approximately 50-80% of infants shed the virus after the first dose. A study in Singapore found that 80% of infants shed the virus by 7 days after vaccination, and 20% continue to shed it a month after vaccination. A study in the Dominican Republic found that 19% of unvaccinated twins contracted the vaccine strain from their vaccinated brothers.

- After the first dose of Rotatec, 13% of babies shed the virus.

Here it is reported that 21% of babies shed the virus after Rotatek, and here that 87%.

It reports that among premature babies, 53% shed the virus after Rotatek.

- Isolation of the vaccine virus and its spread is believed to be an unwanted side effect. However, it also has potential benefits. Infection with the unvaccinated will develop immunity in them, just as happens with the polio vaccine. This effect will be particularly beneficial in poor countries, where vaccination coverage is low, mortality is high, and there are few immunodeficient people. Of course, in developed countries, where mortality is low and there are many immunodeficient people and most people prefer to avoid risk, isolation of vaccine strains can be seen as a hindrance.

- There are 100 billion viral particles in 1 gram of feces from an infected child. Only 10 particles are sufficient for infection. Therefore, adults who change diapers to babies run the risk of becoming infected themselves. Immunodeficient people should not change diapers for an vaccinated infant, especially during 2 weeks after Rotatek, and 4 weeks after Rotarix.

9. Effect of exclusive peastfeeding on rotavirus infection among children. (Krawczyk, 2016, Indian J Pediatr)

Exclusive breastfeeding reduces the risk of rotavirus infection by 38%. Also: [1], [2], [3], [4], [5], [6], [7], [8].

It reports that mothers in Sweden had significantly more antibodies against rotavirus in breast milk in the spring than in the fall.

It reports that blood zinc levels correlate with protection against rotavirus. Late vaccinations (at 17 weeks) are more effective than vaccinations at 10 weeks.

10. Inhibitory effect of peast milk on infectivity of live oral rotavirus vaccines. (Moon, 2010, Pediatr Infect Dis J)

In poor countries, rotavirus vaccines are less immunogenic and less effective than in developed countries. If in Finland Rotarix causes an immune reaction in more than 90% of babies, in South America only 70%, and in South Africa, Malawi, Bangladesh and India - in 40-60%. Other oral vaccines (for polio and cholera) are also less effective in poor countries.

Why this is happening is not yet known, but one possible explanation is that mothers in these countries are more likely to breastfeed their babies during vaccination. Also, mothers in poor countries are more likely to have natural immunity to rotavirus, which is expressed in more antibodies in breast milk, and IgG antibodies transmitted through the placenta.

The authors took breast milk samples from India, Vietnam, South Korea and the United States and tested if it has an inhibitory effect on rotavirus.

It turned out that breast milk samples from India had the most antibodies to rotavirus, milk from Vietnam and South Korea had fewer antibodies, and milk from the United States had the least.

The authors recommend developing parenteral rotavirus vaccines and investigating whether limiting hepatitis B during vaccination would affect its immunogenicity. 1 more].

Here it is reported that abstaining from hepatitis B one hour before and one hour after vaccination does not affect the immunogenicity of the vaccine in any way. More: [1], [2].

11. Vaccines for preventing rotavirus diarrhoea: vaccines in use. (Soares-Weiser, 2012, Cochrane Database Syst Rev)

Cochrane Systematic Review. In developed countries, vaccination reduces the risk of diarrhea by about 40% and the risk of severe rotavirus diarrhea by 86%.

Vaccination has not been found to reduce mortality.

Serious adverse events (SAE) were reported in 4.6% of the Rotaryx vaccinated and 2.4% of the Rotatec vaccinated. Similar amounts of SAE were recorded in the "placebo" groups.

12. Cost-effectiveness and potential impact of rotavirus vaccination in the United States. (Widdowson, 2007, Pediatrics)

Vaccination against rotavirus in the United States will prevent 63% of all rotavirus cases, and 79% of all serious cases. This will lead to the prevention of 13 deaths and 44,000 hospitalizations per year.

For a dose of more than $ 12, vaccination would not be economically viable from a public health standpoint, and for a dose of more than $ 42, it would not be socially justified. Today Rotatek costs $ 69- $ 83 per dose and Rotarix $ 91- $ 110. 1 more].

13. Effectiveness of monovalent rotavirus vaccine (Rotarix) against severe diarrhea caused by serotypically unrelated G2P [4] strains in pazil. (Correia, 2010, J Infect Dis)

In Brazil, the rotavirus strain G2P [4], which occurred in 19% -30% of cases before vaccination, replaced all other strains 15 months after the start of vaccination. The vaccine (Rotarix) efficacy against this strain was 77% among children 6-11 months old, and -24% (negative) among children over 12 months old. More: [1], [2].

It reports that after the start of vaccination in Brazil, the usual strains of rotavirus were replaced by a new strain, G12P [8]. Strain changes have also occurred in Paraguay and Argentina.

14. Effectiveness of the monovalent rotavirus vaccine in Colombia: a case-control study. (Cotes-Cantillo, 2014, Vaccine)

Vaccine efficacy (Rotarix) in Colombia among children 6-11 months of age was 79%; from severe cases of diarrhea 63%; and 67% of very severe cases.

Efficacy in children over 12 months of age was -40%; from severe cases -6%; and from very severe cases -156% (negative efficiency).

The overall vaccine efficacy for all ages was -2%; from severe cases -54%; and from very severe cases -114% (negative efficiency).

It reports that in central Australia the effectiveness of two doses of Rotarix was 19% and that one dose was not effective.

It reports that there is no correlation between the amount of antibody produced and the clinical efficacy of the vaccine.

15. Differentiation of RotaTeq® vaccine strains from wild-type strains using NSP3 gene in reverse transcription polymerase chain reaction assay. (Jeong, 2016, J Virol Methods)

The authors analyzed the stool of 1,106 infants with gastroenteritis and found group A rotaviruses in a quarter of them. 13.6% of the detected strains were vaccine.

16. Detection of rotateq vaccine-derived, double-reassortant rotavirus in a 7-year-old child with acute gastroenteritis. (Hemming, 2014, Pediatr Infect Dis J)

Since the rotavirus genome consists of separate segments, when two different strains of the virus infect the same cell, they can exchange segments and create a new strain. This is the same reassortment that happens uncontrollably.

A case of gastroenteritis in a seven-year-old girl is reported here. A rotavirus strain was isolated from her stool, which was the reassortment of two other human-bovine strains from the Rotatek vaccine. However, the girl was not vaccinated against rotavirus. Moreover, she did not contact anyone who was vaccinated. Her two brothers also had similar symptoms of gastroenteritis, they were also not vaccinated, and did not come into contact with vaccinated.

The isolated reassortant virus strain was found to be stable and highly infectious. The authors believe that this new virus is most likely circulating among the population. Previously, reassortant strains have already been isolated, but only from recently vaccinated Rotatecs: [1], [2], [3].

It reports on the discovery of new strains from the reassortment of the wild virus with the Rotarix vaccine strain.

It reports that 17% of children shed the virus after vaccination, and 37% of them shed the reassortant virus twice. Some children shed the virus long after vaccination, from 9 to 84 days after the last dose.

17. Vaccine-derived NSP2 segment in rotaviruses from vaccinated children with gastroenteritis in Nicaragua. (Bucardo, 2012, Infect Genet Evol)

The authors analyzed the rotavirus genome in vaccinated children with gastroenteritis in Nicaragua, and discovered new viral strains that were formed by reassortment between the wild strain and the vaccine strains from Rotatek.

18. Identification of strains of RotaTeq rotavirus vaccine in infants with gastroenteritis following routine vaccination. (Donato, 2012, J Infect Dis)

Among children who had diarrhea within two weeks after vaccination, 21% were sick from the vaccine strain. Of the isolated vaccine strains, 37% were reassortant strains from the two Rotatek vaccine strains.

nineteen. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. (Stene, 2006, Am J Gastroenterol)

Frequent rotavirus infections are associated with an increased risk of celiac disease.

HLA-DQ2 (a gene associated with celiac disease) is found in 20-30% of healthy white people. However, celiac disease affects less than 1% of the population. 1 more].

20. Rotavirus immunization and type 1 diabetes mellitus: A nested case – control study. (Chodick, 2014, Pediatric Infectious Disease)

The incidence of type 1 diabetes among children under 18 in Israel increased by 6% per year between 2000 and 2008. And among children under 5 years old, it has grown by 104% in 6 years. The authors suggested that viral infections are a factor in the disease, which suggests that vaccination against rotavirus may reduce the risk of diabetes. It turned out, however, that the vaccinated got type 1 diabetes 7.4 times more often than the unvaccinated.

21. Rotavirus vaccines in France: because of three infant death and too many serious side effects vaccines are no longer recommended for routine children immunization. (Michal-Teitelbaum, 2015, BMJ)

Since the start of the rotavirus vaccination in France, 508 side effects (201 of which are serious) have been reported, and 47 cases of intussusception. 2 babies died of intussusception and another died of necrotizing enterocolitis. In the five years prior to vaccination, France had recorded only one death from intussusception.

Therefore, the rotavirus vaccine was not included in the national immunization schedule, and is not funded by the state.

In clinical trials of vaccines, vaccination has not been found to reduce overall mortality, either in developed or developing countries.

22. Merck reports that in clinical trials of Rotatek, the risk of epileptic seizure in vaccinated people was increased 2-fold compared to the "placebo" group. Kawasaki syndrome was reported in 5 Rotatecs vaccinated and 1 in the placebo group. Among premature infants, serious negative cases were reported in 5.5% of vaccinated children and in 5.8% of those receiving "placebo".

GSK reports that in the Rotarix clinical trials, mortality was 0.19% in the vaccinated group and 0.15% in the placebo group. The risk of Kawasaki syndrome in those vaccinated was increased by 71%.

It reports that in the largest clinical trial, Rotarix (63,000 children), there were 2.7 times more pneumonia deaths in the vaccinated group than in the placebo group. The FDA believes this is most likely an accident. It is possible that the vaccine increases the risk of Kawasaki syndrome. More [1], [2].

23. Screening of viral pathogens from pediatric ileal tissue samples after vaccination. (Hewitson, 2014, Adv Virol)

In 2010, a group of independent researchers accidentally discovered porcine circovirus PCV1 in the Rotarix vaccine, and the FDA decided to suspend the vaccination. The FDA initially stated that Rotatec did not contain swine virus, but two months later it was discovered that Rotatec contained two swine viruses, PCV1 and PCV2. The FDA convened a committee that concluded that these viruses are most likely harmless to humans, and that the benefits of vaccination outweigh the hypothetical harms. The committee also recommended that manufacturers develop vaccines free of swine viruses. One week after the virus was discovered in Rotatek, the FDA recommended that pediatricians continue to vaccinate with both vaccines. Eight years have passed since then, but manufacturers are in no hurry to develop vaccines without swine viruses.

In this study, the authors wanted to determine if swine viruses multiply in the human intestine. They did not find swine viruses, but they did find the endogenous M7 baboon virus in the Rotatek vaccine, which probably got there from the kidney cells of African green monkeys, on which the virus for the vaccine is grown.

The Chinese vaccine uses a sheep strain of rotavirus, which is grown on the kidney cells of cows, and the pig virus was not found in the vaccines.

It reports that the PCV2 swine virus, which has been known for 40 years and was harmless, suddenly mutated, spread throughout the world, piglets began to get sick with it, and it became fatal to pigs. 1 more]

24. Intussusception risk after rotavirus vaccination in U. S. infants. (Yih, 2014, N Engl J Med)

The Rotatek vaccine is associated with a nine-fold risk of intussusception (1 in 65,000). This is an order of magnitude lower than the risk from a withdrawn Rotashield vaccine (1-2 / 10,000).

25. Risk of intussusception after monovalent rotavirus vaccination. (Weintraub, 2014, N Engl J Med)

Rotarix increases the risk of intussusception by a factor of 8.4 per week after the first vaccination.

26. Intussusception risk and disease prevention associated with rotavirus vaccines in Australia's National Immunization Program.(Carlin, 2013, Clin Infect Dis)

In Australia, Rotarix increased the risk of intussusception in the week after vaccination by 6.8-fold, and Rotatek by 9.9-fold.

Here it is reported that in Mexico, Rotarix increased the risk of intussusception by a factor of 6.5.

27. Risk of intussusception following rotavirus vaccination: An evidence based meta-analysis of cohort and case-control studies. (Kassim, 2017, Vaccine)

Meta-analysis of 11 studies. The first dose of rotavirus vaccine increases the risk of intussusception by 3.5-8.5 times.

More studies confirming an increased risk of intussusception after vaccination: [1], [2], [3], [4], [5].

It reports that the number of cases of intussusception in the studies is likely to be underreported by 44%.

28. Rotavirus vaccine and intussusception: how much risk will parents in the United States accept to obtain vaccine benefits? (Sansom, 2001, Am J Epidemiol)

Despite the obvious benefits of vaccination, no vaccine is completely safe. Postclinical studies have shown that a newly licensed rotavirus vaccine increases the risk of intussusception. However, it is not known what the risk would be for parents, and how much they would agree to pay for such a vaccine.

To achieve 50% coverage, parents are willing to tolerate 2,897 intussusceptions per year, resulting in 579 surgeries and 17 additional deaths. And to achieve 90% coverage, parents are willing to tolerate no more than 1,794 cases of intussusception, including 359 surgeries and 11 vaccine deaths.

Twenty children die without vaccination from rotavirus.

The lower the parents' income, the more risk they accept.

Parents are willing to pay $ 110 for three doses of the risk-free vaccine, but only $ 36 for three doses of the risky vaccine.

Other studies have already found that parents prefer death from disease over vaccines, and this study confirms this fact.

29. Post-rotavirus vaccine intussusception in identical twins: A case report. (La Rosa, 2016, Hum Vaccin Immunother)

Two twins were vaccinated with Rotarix, a week later, one of them developed symptoms of intussusception and was urgently operated on. A few hours after the operation, the other twin developed similar symptoms and was also operated on. But not so urgent.

30. An infant with acute gastroenteritis caused by a secondary infection with a Rotarix-derived strain. (Sakon, 2017, Eur J Pediatr)

A two-month-old girl in Japan was vaccinated with Rotarix, and 10 days later, her two-year-old sister was hospitalized with severe gastroenteritis. It turned out that she had contracted from her sister a vaccine strain of the virus that mutated.

Here is the exact same case reported in the United States with the Rotatek vaccine. The vaccinated baby 10 days later infected his brother with a rotavirus strain reassorted from two vaccine strains.

31. Persistent rotavirus vaccine shedding in a new case of severe combined immunodeficiency: A reason to screen. (Uygungil, 2010, J Allergy Clin Immunol)

Immunodeficient babies can suffer from severe gastroenteritis for a long time after vaccination. However, at the age of two months when the vaccination is given, it remains to be seen whether the infant is immunodeficient or not. The authors propose to screen children for genetic birth defects before vaccination. 1 more].

32. In the 10 years between 2007 and 2016, VAERS recorded 514 deaths and 230 disabilities following the rotavirus vaccine. Before the start of vaccination, 20 deaths were recorded per year, that is, 1: 200, 000 (and even they, not the fact that it was from rotavirus).

With VAERS accounting for 1% -10% of all cases, the chance of dying after vaccination is 25-250 times higher than the likelihood of dying from rotavirus.