Ben Swann Reports on The CDC, Vaccines and Autism

Ben Swann Reports on The CDC, Vaccines and Autism

I encourage whoever reads this to check out this article and video on The CDC, Vaccines and Autism: Truth In Media: The CDC, Vaccines and Autism . I tried to post the video here, but I couldn’t find a direct link that was in the right format for WordPress.

Here is the article without the video along with the two links to the documents from Dr. Thompson who is the CDC whistleblower regarding the issue of the relation of the number of Autism cases of African American males under the age of 36 months who received the MMR (Measles, Mumps, Rubella) vaccine.

The debate over whether vaccines cause autism has become one of the most controversial disputes in this country. In this episode of Truth In Media, the focus is not on whether vaccines are responsible for autism. The issue at hand here is a study that was performed at the CDC and the question of whether the agency was complicit in a cover-up over a decade ago.

For nearly two years, Truth In Media has explored the allegations of Dr. William Thompson, a CDC scientist who came forward in 2014, hired a whistleblower attorney, and claimed that important data regarding a study on vaccines and autism was eliminated.
Thompson’s claims have led to a divide among Americans, with some believing that Thompson’s allegations are credible and should be investigated further, and others convinced that the documents Thompson handed over mean absolutely nothing. In December 2015, Ben Swann was the first journalist to obtain the documents from Congressman Bill Posey.

In this episode, Swann further examines not only Thompson’s claims, but also the documents related to the study, with the assistance of doctors, journalists, authors and former CDC specialists who joined Swann in discussing every document that was handed over.

Update, January 26, 2016, 2:16 p.m.: Due to a high volume of requests, the CDC documents given to Truth In Media are available below, split into two folders.

Click here to download Folder 1.

Click here to download Folder 2.

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Endocrine Disruption and Cytotoxicity of glyphosate and roundup in Human JAr Cells in Vitro

Endocrine Disruption and Cytotoxicity of glyphosate and roundup in Human JAr Cells in Vitro

by GM Watch

Findings of new study need confirmation in animal tests

Roundup is an endocrine disruptor and is toxic to human cells in vitro (tested in culture dishes in the laboratory) at levels permitted in drinking water in Australia, a new study has found.

This is the first study to examine the effects of glyphosate and Roundup on progesterone production by human female cells in an in vitro system that models key aspects of reproduction in women.

Glyphosate alone was less toxic to human cells than glyphosate in a Roundup formulation; both glyphosate and Roundup caused cell death which resulted in decreased progesterone levels – a form of hormone/endocrine disruption. Endocrine disruption did not precede the toxicity to cells but occurred after it. The decreases in progesterone concentrations were caused by reduced numbers of viable cells.

A 24h exposure to a concentration of glyphosate (in Roundup) similar to that recommended as an acceptable level for Australian drinking water caused significant toxicity to the cells in vitro, which supports a call for long-term in vivo (in live animals) studies to characterise the toxicity of Roundup.

The possibility that Roundup has endocrine disrupting activity independent of its ability to kill or disable cells needs further study.

Endocrine disruption and cytotoxicity of glyphosate and roundup in human JAr cells in vitro

Fiona Young, Dao Ho, Danielle Glynn and Vicki Edwards
Department of Medical Biotechnology, Flinders University, Adelaide, South Australia
Integr Pharm Toxicol Genotoxicol, 2015 Volume 1(1): 12-19
doi: 10.15761/IPTG.1000104

Abstract

The toxicity of the active molecule in herbicides has been used to determine safe concentrations, because other components are considered inert. Roundup, which contains the active molecule Glyphosate, was described as an endocrine disrupter because non-cytotoxic concentrations inhibited progesterone synthesis in vitro. Human chorioplacental JAr cells synthesise progesterone, and increase synthesis when stimulated by chorionic gonadotrophin (hCG), or the transduction molecule cAMP.

JAr cells were exposed to two Roundup formulations, and compared with the same concentrations of glyphosate ± cAMP, or ± hCG for 1, 4, 24, 48 or 72h. The surviving viable cells were quantified using an MTT assay, and progesterone was measured in an ELISA. hCG and cAMP stimulated progesterone synthesis by cells in vitro as expected. In contrast to previous reports, JAr cell death preceded decreased progesterone synthesis, and steroidogenesis was unaffected by low, non-cytotoxic concentrations of Roundup or glyphosate. Roundup was more cytotoxic than glyphosate alone; the 24h EC50 was 16mM for glyphosate, but 0.008mM when glyphosate was in a 7.2g/L Roundup formulation. Significant cytotoxicity was caused by glyphosate in Roundup (p<0.01) after 24h, and cytotoxicity was observed in vitro after exposure to a range of concentrations comparable to the Australian Drinking Water Guidelines.

Endocrine disruption effects were secondary to cytotoxicity. Roundup was more cytotoxic than the same concentration of glyphosate alone, indicating that the other constituents of the herbicide are not inert. There is a compelling need to conduct in vivo studies to characterise the toxicity of glyphosate in a Roundup formulation, to facilitate re-evaluation of existing public health guidelines.

Source.

Read the full study.

 

– See more at: http://healthimpactnews.com/2015/study-roundup-causes-cell-death-to-human-placenta-cells-at-levels-allowed-in-drinking-water/#sthash.AlrycuWi.dpuf

Health Impact News

Pertussis Infection in Fully Vaccinated Children in Day-Care Centers, Israel

Pertussis Infection in Fully Vaccinated Children in Day-Care Centers, Israel

Pertussis1

On This Page

Isaac Srugo*Comments to Author , Daniel Benilevi*, Ralph Madeb*, Sara Shapiro†, Tamy Shohat‡, Eli Somekh§, Yossi Rimmar*, Vladimir Gershtein†, Rosa Gershtein*, Esther Marva¶, and Nitza Lahat†
Author affiliations: *Department of Clinical Microbiology, Bnai Zion Medical Center, Haifa, Israel; †Serology Laboratory, Carmel Medical Center, Haifa, Israel; ‡Israel Center for Disease Control, Tel Aviv, Israel; §Wolfson Medical Center, Tel Aviv, Israel; ¶Public Health Laboratories, Jerusalem, Israel

Suggested citation for this article

Abstract

We tested 46 fully vaccinated children in two day-care centers in Israel who were exposed to a fatal case of pertussis infection. Only two of five children who tested positive for Bordetella pertussis met the World Health Organization’s case definition for pertussis. Vaccinated children may be asymptomatic reservoirs for infection.

Pertussis, an acute disease of the upper respiratory tract caused by the gram-negative bacillus Bordetella pertussis, lasts 6 to 8 weeks and has three clinical stages. The initial (catarrhal) stage resembles a common cold with a mild cough. The second (paroxysmal) stage is characterized by episodes of repetitive coughing during a single expiration, followed by a sudden inspiration that generates the typical “whoop.” The final (convalescent) stage, which lasts 1 to 2 weeks, marks a decrease in the severity and frequency of the cough.

Since the introduction of routine childhood vaccine, pertussis has been considered preventable, and pertussis-associated illness and deaths are uncommon (2). However, vaccine-induced immunity wanes after 5 to 10 years, making the vaccinated host vulnerable to infection (3). This susceptibility has been described in outbreaks of pertussis infection in highly vaccinated populations (36).

A recent study by Yaari et al. showed that infection in a vaccinated person causes milder, nonspecific disease, without the three classical clinical stages(7). Whooping cough is seen in only 6% of such cases; instead, the illness is characterized by a nonspecific, prolonged cough, lasting several weeks to months. Because of these atypical symptoms, pertussis infection is underdiagnosed in adults and adolescents, who may be reservoirs for infection of unvaccinated infants (810). In a study in France, up to 80% of infections in unvaccinated children were acquired from siblings and parents, suggesting that adults and even young siblings play a fundamental role in the transmission of pertussis (11).

We demonstrated B. pertussis infection in fully vaccinated children ages 2-3 years and 5-6 years who had contact with an infected child. We investigated whether younger or recently vaccinated children may be protected from classical clinical illness but remain susceptible to infection and become asymptomatic carriers.

The Study

We examined the family of a 4-month-old infant who died of pertussis in Israel, as well as children at two day-care centers that two siblings had attended during the infant’s illness. The two siblings, ages 2 and 5 years, attended different day-care centers, for ages 2-3 years and 5-6 years, respectively. Both siblings continued to attend the centers despite paroxysmal cough for 4 to 5 weeks. Thirty other children attended the day-care center for the 2- to 3-year-old group. Sixteen other children attended the center for the 5- to 6-year-old group.

Thumbnail of Timeline of pertussis infection in children in two day-care centers, IsraelFigure. Timeline of pertussis infection in children in two day-care centers, Israel

In the infant’s family, a third sibling, age 11 years, also had a paroxysmal cough of 4 to 5 weeks duration. The 35-year-old mother had a 3-month history of persistent cough. An 18-year-old aunt, who took care of the infant and lived in the same house, reported a mild respiratory illness without paroxysmal cough. None of the family members had a whooping episode, cyanosis, or pneumonia (Figure).

All the children in the day-care centers had been immunized in infancy with all four doses of Pasteur diphtheria-tetanus toxoid pertussis (DTP) vaccine, which includes a booster dose at 12 months of age. The Pasteur vaccine contains 1 immunization dose (ID) of purified diphtheria toxoid, 1 ID of purified tetanus toxoid, and >4 IU of B. pertussis. All family members of the infant were also fully vaccinated with four doses of DTP. The infant had received only the first dose of vaccine at 2 months of age.

The five family members of the infant and the 46 children in the two day-care centers were tested for B. pertussis. Two nasopharyngeal specimens were taken with Dacron swabs (Medical Wire, MEDECO, Corsham, UK); one specimen was used for culture and the other for polymerase chain reaction (PCR) testing. The culture specimen was immediately spread on charcoal agar plates (Hy Labs, Rehovot, Israel), which were incubated at 37°C for 14 days. Serum samples were also taken from every study participant for specific testing for immunoglobulin (Ig) M, IgA, and IgG antibodies to B. pertussis by an enzyme immunoassay (EIA) with whole-cell antigens (Panbio, East Brisbane, Australia) (12). Primers for the repeated insertion sequences were used in a semi-nested PCR assay (1314). The upstream primer sequence gATTCAATAggTTgTATgCATggTT and downstream primer AATTgCTggACCAT TCgAgTCgACG were used in the first PCR, which included 5 µL sample DNA, reaction buffer (10 mM Tris-HCl, 50 mM KCl, 1.5 mM MgCl2, 0.1% Triton X-100), 1 µM of each primer, 200 µM deoxynucleotide triphosphate, and 1 U Taq polymerase (Boehringer Mannheim, Germany) in a 25-µL volume (14). Statistical analysis was performed by the two-tailed Fischer’s exact test.

A person with positive PCR results was considered to have B. pertussis colonization of the nasopharynx. A person with positive IgM serum antibodies was considered to have had a recent infection. There were no culture-positive results, and nasopharyngeal aspirates were not available from the infant. Positivity by PCR or IgM did not indicate presence of symptoms.

Information on clinical symptoms was obtained from each person by a detailed questionnaire. The children in the day-care centers were followed clinically for 8 weeks after laboratory testing. All family members had been treated with erythromycin before testing, but no antibiotics were administered to the children in the day-care centers.

Eleven percent of the children in the two day-care centers were PCR positive, indicating nasopharyngeal colonization: 4 (25%) of the 16 5- to 6-year-old and 1 (3%) of the 30 2- to 3-year-old children (p <.05). Nine (55%) 5- to 6-year-old children were positive for serum IgM antibodies, and 4 (25%) were IgA positive. Three (10%) of the 2- to 3-year-old children were IgM positive, and 1 (3%) had IgA antibodies. Nasopharyngeal colonization was found more frequently in the 5- to 6-year-old than in the 2- to 3-year-old children (4/16 vs. 1/30, p <.05). This trend was also constant with IgM and IgA serum antibodies (9/16 vs. 3/30, p <.001 and 4/16 vs. 0/30, p <.01, respectively). In the index family, four of five members were positive by PCR, including all three siblings of the infant and the 18-year-old aunt. The 35-year-old mother, who was treated with erythromycin before testing, was negative by PCR. All five family members, including the mother, had high levels of IgM antibodies, indicating recent infection. The 4-month-old infant was seronegative for all subclasses of Ig antibodies to B. pertussis. No cultures were grown from the three groups.

According to a modified World Health Organization (WHO) case definition, two (11%) of the five children colonized with B. pertussis in the two day-care centers had the typical course of pertussis infection, with 3 weeks of paroxysmal cough (Table) (1). The other three children who were positive by PCR had only a mild, nonspecific cough during follow-up.

Conclusions

The effects of whole-cell pertussis vaccine wane after 5 to 10 years, and infection in a vaccinated person causes nonspecific symptoms (37). Vaccinated adolescents and adults may serve as reservoirs for silent infection and become potential transmitters to unprotected infants (311). The whole-cell vaccine for pertussis is protective only against clinical disease, not against infection (1517). Therefore, even young, recently vaccinated children may serve as reservoirs and potential transmitters of infection.

We used PCR, EIA, and culture to confirm B. pertussis infection in two highly vaccinated groups of children in two day-care centers. Three (10%) of 30 2- to 3-year-old children were seropositive for recent infection; one had nasopharyngeal colonization and a clinical illness that met the modified WHO case definition. In the day-care center for the 5- to 6-year-old group, 9 (55%) of 16 children were IgM positive, 4 (25%) of whom had nasopharyngeal colonization. Of these four children, three had nonspecific cough, and only one met the modified WHO definition for pertussis. None of the children in our study, including those who met the WHO definition, had been examined by a physician before our investigation.

Children who were seropositive and remained both asymptomatic and PCR negative probably had sufficient immunity from vaccines or natural boosters to protect them against persistent colonization and clinical disease. Their seropositivity could not be due to vaccine because the children were tested more than a year after having been vaccinated. Yet not all the children were protected from infection and from colonization with the bacteria. Whether a child who is serologically or PCR positive for pertussis and is clinically asymptomatic is a potential transmitter of infection has not been established. What is certain, however, is that vaccine-induced immunity against infection does not persist throughout adulthood. In France, booster vaccinations have been recommended for adolescents and teenagers (18). We found that immunity does not even persist into early childhood in some cases. We also observed that DPT vaccine does not fully protect children against the level of clinical disease defined by WHO. Our results indicate that children ages 5-6 years and possibly younger, ages 2-3 years, play a role as silent reservoirs in the transmission of pertussis in the community. More studies are needed to find the immunologic basis of protection against infection and colonization and thus an effective way to eradicate pertussis.

Dr. Srugo is a senior lecturer and director of the Clinical Microbiology and Pediatric Infectious Disease unit at the Bnai Zion Medical Center, Haifa, Israel.

References

  1. WHO meeting on case definition of pertussis: Geneva 10-11 January, 1991. Geneva: World Health Organization, 1991:4-5 (issue no. MIN/EPI/PERT/91.1)

  2. Cherry JD. The epidemiology of pertussis and pertussis immunization in the United Kingdom and the United States: a comparative study. Curr Probl Pediatr. 1984;14:178. DOIPubMed

  3. Jenkinson D. Duration of effectiveness of pertussis vaccine: evidence from 10-year community study. [Clin Res Ed]. BMJ. 1988;296:6124.DOIPubMed

  4. Christie CD, Marx ML, Marchant CD, Reising SF. The 1993 epidemic of pertussis in Cincinnati: resurgence of disease in a highly immunized population of children. N Engl J Med. 1994;331:1621. DOIPubMed

  5. Rosenthal S, Strebel P, Cassiday P, Sanden G, Brusuelas K, Wharton M. Pertussis infection in young adults during the 1993 outbreak in Chicago. J Infect Dis. 1995;171:16502.PubMed

  6. De Melker HE, Conyn Van Spaendonck MA, Rumke HC, van Wijngaarden JK, Mooi FR, Schellekens JF. Pertussis in the Netherlands: an outbreak despite high levels of immunization with whole-cell vaccine. Emerg Infect Dis. 1997;3:1758. DOIPubMed

  7. Yaari E, Yafe-Zimerman Y, Scwartz SB, Slater PE, Shvartzman P, Andoren N, Clinical manifestations of Bordetella pertussis infection in immunized children and young adults. Chest. 1999;115:12548. DOIPubMed

  8. Aoyama T, Takeuchi Y, Goto A, Iwai H, Murase Y, Iwata T. Pertussis in adults. Am J Dis Child. 1992;146:1636.PubMed

  9. Cromer BA, Boydos J, Hackell J, Mezzatesta J, Dekker C, Mortimer EA. Unrecognized pertussis infection in adolescents. Am J Dis Child.1993;147:5757.PubMed

  10. Nelson JD. The changing of epidemiology of pertussis in young infants: the role of adults as reservoirs of infection. Am J Dis Child.1978;132:3713.PubMed

  11. Baron S, Njamkepo E, Grimprel E, Begue P, Desenclos JC, Drucker J, Epidemiology of pertussis in French hospitals in 1993 and 1994: thirty years after a routine vaccination. Pediatr Infect Dis J. 1998;17:4128. DOIPubMed

  12. He Q, Mertsola J, Soini H, Skurnik M, Ruuskanen O, Viljanen MK. Comparison of polymerase chain reaction with culture and enzyme immunoassay for diagnosis of pertussis. J Clin Microbiol. 1993;31:6425.PubMed

  13. He Q, Mertsola I, Soini H, Viljanen MK. Sensitive and specific polymerase chain reaction assays for detection of Bordetella pertussis in nasopharyngeal specimens. J Pediatr. 1994;124:4216. DOIPubMed

  14. Lichtinghagen R, Diedrich-Glaubitz R, von Horsten B. Identification of Bordetella pertussis in nasopharyngeal swabs using a polymerase chain reaction: evaluation of detection methods. Eur J Clin Chem Clin Biochem. 1994;32:1617.PubMed

  15. Fine PEM, Clarkson JA. The recurrence of whooping cough: possible implications for assessment of vaccine efficacy. Lancet. 1982;l:6669.DOIPubMed

  16. Long SS, Welkon CJ, Clark JL. Widespread silent transmission of pertussis in families: antibody correlates of infection and symptomatology. J Infect Dis. 1990;161:4806.PubMed

  17. Minh NNTM, He Q, Edelman K, Olander RM, Viljanen MK, Arvilommi H, Cell-mediated immune response to antigens of Bordetella pertussis and protection against pertussis in schoolchildren. Pediatr Infect Dis J. 1999;18:36670. DOIPubMed

  18. Grimprel E, Baron S, Levy-Bruhl D, Garnier JM, N’jamkepo E, Guiso N, Influence of vaccination coverage on pertussis transmission in France.Lancet. 1999;354:1699700. DOIPubMed

Figure

Table

Suggested citation: Srugo I, Benilevi D, Madeb R, Shaprio S, Shohat T, Somekh E, et al. Pertussis Infection in Fully Vaccinated Children in Day-Care Centers, Israel. Emerg Infect Dis [serial on the Internet]. 2000, Oct [date cited]. Available from http://wwwnc.cdc.gov/eid/article/6/5/00-0512

DOI: 10.3201/eid0605.000512

Table of Contents – Volume 6, Number 5—October 2000

Article copied from CDC.GOV

Polish Study of Neurologic Adverse Events Following Vaccination

Polish Study of Neurologic Adverse Events Following Vaccination

Prog Health Sci 2012, Vol 2 , No1 Neurologic adverse events vaccination 129 Neurologic adverse events following vaccination Sienkiewicz D.*, Kułak W., Okurowska-Zawada B., Paszko-Patej G. Department of Pediatric Rehabilitation of the Medical University of Bialystok, Poland

ABSTRACT __________________________________________________________________________________________

The present review summarizes data on neurological adverse events following vaccination in the relation to intensity, time of onset, taking into account the immunological and non-immunological mechanisms. The authors described the physiological development of the immune system and the possible immune system responses following vaccination. Toxic property of thimerosal – a mercury-containing preservative used in some vaccines was presented. The neurological complications after vaccination were described. The role of vaccination in the natural course of infectious diseases and the current immunizations schedule in Poland was discussed.

Key words: vaccination, neurologic adverse events following vaccination, immunization schedules __________________________________________________________________________________________ *Corresponding author: Department of Pediatric Rehabilitation Medical University of Białystok 17 Waszyngtona str, 15-836 Białystok Poland E-mail: sdorota11@op.pl (Dorota Sienkiewicz) Received: 29.01.2012 Accepted: 22.02.2012 Progress in Health Sciences Vol. 2(1) 2012·pp 129-141. © Medical University of Bialystok, PolandProg Health Sci 2012, Vol 2 , No1 Neurologic adverse events vaccination 130

INTRODUCTION

Adverse reactions In developed countries, the schedules of mandatory and recommended vaccination for children contain more and more components with a specific emphasis on the co-administration of multiple antigens in combined form. This direction on the one hand provides many benefits and on the other carries an increased risk of side effects, the immunopathogenesis of which is not fully explained in many cases [1]. An adverse event following immunization (AEFI) is an undesirable side effect occurring after the administration of a vaccine [2]. It is a temporary, local or general reaction of the organism to an administered vaccine. A postvaccinal complication (PC) is associated with an excessive or pathological reaction with the characteristics of postvaccinal disease, which in extreme cases can lead to permanent damage, threat to life or even death [3]. Complications affecting the nervous system raise the most controversy; the more so, as the children subjected to vaccination are healthy.

In annex no. 1 to the Ordinance of the Minister of Health of 23rd December 2002 on adverse events following vaccination (Journal of Law from 31/12/2002, no. 241, item 2097, as amended. Journal of Law from 2005, no. 232, item 1973), the following categories of AEFI are presented [4].

1) Local reactions, including:

  • a) local reactions after the BCG vaccine,
  • b) swelling,
  • c) lymphadenopathy,
  • d) abscess at the injection site;

2) Postvaccinal adverse events of the central nervous system:

  • a) encephalopathy,
  • b) febrile convulsions,
  • c) non-febrile convulsions,
  • d) paralytic poliomyelitis caused by vaccine virus,
  • e) encephalitis,
  • f) meningitis,
  • g) Guillain – Barre syndrome;

3) Other adverse events following immunization:

  • a) joint pain,
  • b) hypotonic-hyporesponsive episode
  • c) fever above 39⁰C
  • d) thrombocytopenia,
  • e) continuous inconsolable crying.

Other classifications of postvaccinal reactions can be found in the literature, some of which put an emphasis on the neurological symptoms, while others emphasize the immunological mechanisms.

Byers et al. describing neurological complications, have included as “minor” – mild or severe postvaccinal reactions, occurring up to 48 hours after injection and disappearing without leaving permanent sequelae, the following:

  • prolonged crying,
  • restlessness and hyperactivity,
  • apathy with increased sleepiness,
  • high body temperature,
  • a temporary mild increase in intracranial pressure manifested by a throbbing crown of the head,
  • “cerebral cry” (sometimes included among “major” complications) [5-7].

Among the “major” neurological complications, usually manifesting more than 48 hours after vaccination and which might be the cause of permanent damage to the central nervous system (CNS), the following are listed:

  • seizures – especially if there is no increase in body temperature,
  • hypotonic-hyporesponsive episodes,
  • postvaccinal encephalitis,
  • postvaccinal encephalopathy [6, 8-11]
  • and autism [10, 12-14].

Konior and Strózik [7] have proposed their own classification of postvaccinal reactions taking into account the contribution of the immune system in the vaccinated children. They divided the adverse events into two groups:

1. related to the immune system – patients with immunodeficiencies (mainly cellular) and atopic patients with hypersensitivity to certain vaccine components

2. unrelated to the immune system – patients whose postvaccinal reactions may be related to the toxic effects of the vaccine components or may result from the vaccine virus turning virulent, resulting in complete or abortive symptoms of the disease.

Another classification of adverse events following vaccination distinguishes:

Local postvaccinal reactions (redness, swelling, pain at the injection site) occurring particularly often after the administration of live vaccines (10.8% -15.5% of reports) [15]

 Generalized postvaccinal reactions (fever, malaise, muscle pain, joint pain, headaches, flu-like symptoms, local lymphadenopathy, allergic reactions) – usually disappear spontaneously within 3 days of vaccination, do not require treatment [16].

 Early postvaccinal complications – anaphylactic reaction, described in one in about 1 million of vaccinated individuals, occurs most often after immunization against typhoid, tetanus, pertussis, measles, mumps, rubella [16].

 Late and long-term complications – determined by different immunological mechanisms, occur most often after the administration of preparations containing live micro-organisms (e.g., flaccid paralysis after an oral poliovirus vaccine OPV – 10 individuals annually per 1 million people vaccinated) [16].

Prog Health Sci 2012, Vol 2 , No1

Neurologic adverse events vaccination 131

Reports in many Polish and foreign medical journals lead us to conclude that postvaccinal complications among children can be observed in sporadic cases and that they are disproportionate to the benefits of vaccination in the elimination of dangerous diseases in childhood. This article focuses on several aspects related to overall immunization, including: the physiological development of the immune system, the possible immune system responses following vaccination, the site of vaccination in the natural course of infectious diseases and the current immunization schedule in Poland compared with other countries. The immune system in terms of vaccination

Physiology

Immune system functioning in neonates is characterized by complex mechanisms to adapt to the changed conditions of postnatal life. In infancy and early childhood, the individual components of specific and nonspecific immunity gradually develop and mature [17]. The humoral immunity of neonates is acquired and is associated with active transport of maternal immunoglobulin G through the placenta (starting from the end of the first trimester of pregnancy) mainly in the last 5-6 weeks of pregnancy. A neonate’s humoral response is therefore a state of physiological dysimmunoglobulinemia, i.e. it has an average concentration of its own IgG, minimal or low concentrations of IgA, IgM, IgE, IgD [13, 14]. The level of maternal IgG gradually decreases, while the level of the child’s IgG increases reaching approximately 60% of the adult level after 12 months. In the 2-3 month of life, an intersection of curves takes place – the declining curve of maternal IgG concentration and the increasing curve of infant IgG concentration (graph). The infant’s IgG level is the lowest then [18].

Levels of antibodies in the blood serum of the fetus, neonate and infant [18] From a physiological point of view, according to Jakóbisiak’s [18] classification, the group of secondary immunodeficiency disorders includes conditions such as pregnancy and conditions associated with age (neonates, the elderly). Premature babies are a specific group, whose shortened period of maternal IgG influx leads to compromised anti-infective immunity. On the other hand, according to the author, on account of the existing maternal antibodies, vaccination against certain microorganisms administered shortly after birth does not lead to long-lasting immunity. It should be emphasized that the immune system reaches full immunoregulatory and defensive maturity at about 3 years of age [19]. It is well established that early-life immune responses are weaker and of shorter duration than elicited in immunologically mature hosts. Consequently, vaccine efficacy in early infancy (particularly in the first 6 months of age) is limited [20]. Thus, in oder to provoke and sustain an adequate B-cell immune response in a neonate, strong immune adjuvants and repeated closely spaced booster doses are needed [21]. The problem with this approach is two-fold. First, experimental evidence clearly shows, that simultaneous administration of as little as two to three immune adjuvants, or repeated stimulation of the immune system by the same antigen can overcome genetic resistance to autoimmunity [22]. Second,while it is generally accepted that potency and toxicity of immune adjuvants must be adequately balanced so that the necessary immune stimulation is achived with minimal side effects, in practical terms, such a balance is very difficult to achieve. This is because the same adjuvantedmediated mrchanisms which drive to the immunestimulatory effects of vaccines have the capacity to provoke a variety of adverse reactions [23, 24] Vaccinations and immune response A vaccine is defined as a biological preparation containing antigen(s) of microorganisms that cause specific stimulation of the immune response after administration which protects against infection by this microorganism, with safety precautions taken during administration [18, 25].

A vaccine may contain:

  • 1. Microorganism antigens – bacterial or viral (live-attenuated, dead), isolated antigens – proteins, polysaccharides, DNA and anatoxins (diphtheria, tetanus) with retained immunegenicity but devoid of pathogenic properties,
  • 2. Suspension: water, physiological saline, substrate protein, e.g. egg white, gelatin,
  • 3. Preservatives: thiomerosal (mercury), antibiotics, phenol,
  • 4. Adjuvants, the aim of which is to enhance the immunogenicity of the vaccine – aluminum hydroxide or aluminum phosphate are the most commonly used.

Prog Health Sci 2012, Vol 2 , No1 Neurologic adverse events vaccination 132

According to the literature [18], it is believed that vaccines containing live microorganisms are among the most effective means of inducing immunity against infectious disease. Attenuated microorganisms (viruses, BCG mycobacteria) retain the ability to replicate in host cells, which stimulates cytotoxic T lymphocytes (Tc, CD8 +) that destroy cells infected by them. The way of impact of isolated antigens or antigens derived from whole inactivated microorganisms is different. In this case, a stimulation of the auxiliary Th (CD4+) lymphocyte response takes place. Th lymphocytes contain two distinct – in functional terms – subpopulations: Th1 and Th2. According to Jakóbisiak – with some simplification – it can be assumed that the Th1 lymphocytes perform auxiliary functions in cell-type response and Th2 in humoral response [18]. The mechanism of immune response to various types of vaccine antigens, especially to antigens in multicomponent vaccines, is not fully understood and researched.

The vaccination-stimulated Th2 pathway responsible for the production of antibodies, the pathway which predominates in neonates and infants, in the absence of an adequate balance of Th1 response may lead to the development of allergic reactions [25]. This is symptomatic of the fact that allergic diseases are often referred to as “an epidemic of the XXI century” [26, 27]. As stated in the “European Allergy White Paper”, the clinical symptoms of allergy are present in 35% of the population of developed countries, and according to the ISAAC (The International Study of Asthma and Allergies in Childhood) as many as 40%. Allergy is one of the major health problems on par with AIDS, cancer, cardiovascular diseases, injuries and accidents [28 – 30]. According to other authors, a restriction of the natural environmental infections stimulating Th1 response as well as change of their natural course resulting from mass immunization, an increase in general hygiene and widespread use of antibiotics (“Hygiene Theory”) inhibiting and delaying the adjustment of Th2/Th1 could theoretically also contribute to the growth of the risk of allergic diseases [31, 32]. A confirmation of this thesis was the study of Swiss children from anthroposoic backgrounds, in which significantly less atopy was observed than in children from other backgrounds. In this group, a positive correlation of diseases with the MMR vaccination was found [33]. In addition, in a series of papers, Silverberg et al. have shown that wild type varicella zoster virus infection (WTVZV), but not varicella vaccine (VV), protects against asthma and atopic dermatitis (AD) in young children [34, 35]. The protective effect of WTVZV was attributed to its beneficial effect on stimulating Th1-primed immune responses and suppressing allergy-promoting Th2 responses. According to Silverberg et al. [34], ―The introduction of widespread varicella vaccination and resultant decline of WTVZV in the United States may be a contributing factor in the increased prevalence of AD [atopic dermatitis] over the past few decades.‖ Notably, other than not providing an effective stimulus for proper immune system development, recent research has shown that vaccines are actually capable of disrupting it. For example, annual vaccination against influenza has been shown to hamper the development of virusspecific CD8+ T-cell immunity in children [36] From the above observations it is clear that the proper functioning of the immune system involves a delicate balance between the two arms of the immune equilibrium (Th1/Th2), and its tilt to either side can be harmful for the body [30]. Furthermore, it appears that the necessary Th1/Th2 balance is better provided by natural challenges (i.e., in a form of relatively benign childhood diseases such as chickenpox and mumps) rather than vaccination. Recent research by Singh of the International Institute for Brain Research in the USA confirm the veracity of this statement. In the study, serum and cerebrospinal fluid (CSF) were analyzed in terms of viral and autoimmune markers in Prog Health Sci 2012, Vol 2 , No1 Neurologic adverse events vaccination 133 patients with autism compared with a group of healthy children – both groups were vaccinated with MMR (measles, mumps, rubella vaccine) [37]. This is the first of this type of research examining a positive correlation between viral factors (viral serology) and autoimmune factors (brain autoantibodies). It was found that higher levels of measles antibodies were accompanied by Myelin Basic Protein (MBP) autoantibodies in children with autism (Figure.3). A similar serology was found in CSF. Fig. 3. Correlations between MMR antibodies and MBP autoantibodies in autistic and healthy children. (Source: [37] Singh VK. Phenotypic expression of autoimmune autistic disorder (AAD): A major subset of autism. Annals of Clinical Psychiatry, 2009, 21, 3,148-161; with permission: Healthy Impressions) The results in Table 1 show a comparative study of antibodies against other viral pathogens in the studied population of children which confirmed the pathogenic role of the measles strain.

Table 1. Blood serum levels of antiviral antibodies in healthy and autistic children Virus antibody (units)

Measle s Mu mps Rub ella HH V-6 CMV EBV EA EBN A VC A

  • Normal children 3.3±0. 1 2.5± 0.2 3.2± 0.2 1.6± 0.6 0.28 ±0.4 0.5±0 .04 1.2 ±0.2 1.8± 0.3 (n=32) (n= 30) (n=4 5) (n= 37) (n=3 0) (n=4 4) (n=4 4) (n= 44)
  • Autistic children 4.2±0. 1* 2.6± 0.3 3.3 ±0.1 2.2± 5.3 0.23+ 0.3 0.6 ±0.04 0.9± 0.2 1.4± 0.2 (n=87) (n= 32) (n=7 4) (n= 45) (n=3 0) (n=4 4) (n=4 4) (n= 44) p value .003* .76 .98 .5 .37 .76 .21 .15

(Source: [37] Singh VK. Phenotypic expression of autoimmune autistic disorder (AAD): A major subset of autism. Annals of Clinical Psychiatry, 2009, 21, 3,148-161; with permission: Healthy Impressions)

CMV: cytornegalovirus; EA: early antigen; EBNA: Epstein-Barr nuclear antigen; EBV: Epstein-Barr virus; HHV-6: human herpesvirus-6; VCA: viral capsid antigen; *Student t test was used to evaluate significance at a p value < 0.05 Significantly elevated levels of cytokines – IL-2, IL-12, IFN-γ (factors triggering autoimmune response) – and acute phase proteins were also found in patients [37].

According to the authors of this study, subtle changes in the child’s developing brain caused by an autoimmune reaction, changes in the myelin sheath, may ultimately lead to impairment Prog Health Sci 2012, Vol 2 , No1 Neurologic adverse events vaccination 134 of higher brain functions such as speech, communication, social interaction, as well as other neurological symptoms occurring in children with autism. In this study, the measles viruses were researched, but under the immunization program children also receive vaccinations with simultaneous administration of several viral components. What then occurs in the brain of a child? Presently, there are no studies in this area.

In an earlier study concerning postvaccinal adverse events of the immune system, Mannhalter et al. [38] presented an analysis of T lymphocyte (Th1/Th2) subpopulations in healthy adults before and after the administration of a vaccine containing the tetanus toxin. The result was a decrease in the Th1/Th2 ratio after vaccination, with maximum intensity 3 to 14 days after injection. These reports present a picture of neuroimmune disorders which may be the result of vaccinations carried out on an increasingly wider scale. A clear answer to this hypothesis would require both large-scale epidemiological studies as well as in-depth laboratory research. In Poland, multi-antigen combination vaccines are commonly administered at full cost with parental consent. Most often children are immunized at the same time with: diphtheria and tetanus toxoid, acellular pertussis antigen, polio and H.influenzae (Infanrix-IPV+Hib, Pentaxim vaccines) or with an additional antigen of hepatitis B virus (Infanrix hexa vaccine). These vaccinations are repeated from the second month of life 3 times every 6-8 weeks. The recommended vaccinations against rotavirus and pneumococcal (2-3 doses) are also proposed to children under 6 months of age. Together with the tuberculosis and hepatitis B vaccinations administered in the first 24h of life, an infant receives 24-26 doses of xenogenic antigens. According to Tsumiyama et al. [39] systemic autoimmunity appears to be the inevitable consequence of over-stimulating the host’s immune ‘system’ by repeated immunization with antigen. Indeed, in adults multiple vaccinations have been associated with a variety of autoimmune phenolmena [40 – 42], yet children are regularly exposed to a much higher burden of vaccines than adults under the assumption that such exposures are safe [43] . Vaccinations as an important “training” for the immune system lower its threshold of defense responses, which is a measure to prevent the development of infectious diseases. However, a question arises: how will the not fully mature, still developing immune system of a healthy child and the still forming central nervous system respond to such intense stimulation? Is it able to correctly respond with the same protective effect to so many different stimuli? Do the multi-antigen vaccine side effects change compared to the previously used vaccinations and how? Thus far, these questions lack clear answers. Nonetheless, it is important to emphasize that a burgeoning body of evidence shows that immune molecules play integral roles in CNS development, affecting processes such as neurogenesis, neuronal migration, axon guidance, synaptic connectivity and synaptic plasticity [44 – 46]. Despite the dogma that peripheral immune responses do not affect CNS function, substantial evidence points exactly to the contrary [44, 47, 48]. Thus, it is not reasonable to assume that manipulation of the immune system through an increasing number of vaccinations during critical periods of brain development will not result in adverse neurodevelopmental outcomes [43, 49] Neurological symptoms following vaccination

In recent years, attention has been brought to the mercury contained in vaccines as a component with toxic and allergic properties. The mercury compound is found in organic combinations in the form of sodium salt – thimerosal (sodium ethylmercuriothiosalicylate, merthiolate). The incidence of allergy to this compound is variously estimated from 13% in the Netherlands to 21% in Austria. Vaccinations are a primary cause of the initial allergic reactions to thimerosal [50]. Mercury’s neurotoxicity (accumulation in the brain), cardiotoxicity, hepatotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity are mentioned as its toxic activity. It causes, among others, developmental disorders in children and neurodegenerative diseases in adults [7]. According to researchers [51, 52], a manifold incidence increase of psychoneurological diseases such as autism, ADHD, mental retardation, epilepsy and others have been observed all over the world over the past twenty years. As stated, from the 1990s new vaccines for infants containing thimerosal began to be used in America. In the DTP, Hib and Hep B vaccines, children received a dose of 62.5 ug of mercury, which is 125-fold more than the dose considered safe (0.1ug/kg/day). These reports were the reason that Scandinavian countries already prohibited the use of mercury in 1990 [53]. In 2005, a paper was published which describes the sudden death (SUD – Sudden Unexpected Death) of 19 infants within a few hours/days after vaccination with two hexavalent vaccines (DTP-Hib-HepB-IPV). The healthy prior to vaccination children died as a result of postvaccinal cerebral and lung edema and heart attacks. As the authors conclude, despite the lack of direct evidence for a causal relationship of the described SUDs with vaccination, it is a signal that brings to attention the need to monitor the course of vaccination and its complications [54].Prog Health Sci 2012, Vol 2 , No1 Neurologic adverse events vaccination 135

In another study from 2004, Geier et al. [12] confirmed through epidemiological research the direct relationship between increasing doses of thimerosal and the incidence of autism in children in the US from the late 1980s through the mid- 1990s. In addition, there was a potential correlation between the number of primary pediatric measlescontaining vaccines (MMR) administered and the prevalence of autism during the 1980s. Geier et al. [12] also found a statistically significant odds ratios for the development of autism following increasing doses of mercury from thimerosal-containing vaccines (birth cohorts: 1985 and 1990-1995) in comparison to a baseline measurement (birth cohort: 1984). The contribution of thimerosal from childhood vaccines (>50% effect) was greater than that of the MMR vaccine on the prevalence of autism observed in the study. In Poland, according to the documents “Characteristics of Pharmaceuticals”, there are currently several permitted vaccines with significant thimerosal (THIM) content. These are: Euvax (Hepatitis B, LG Life Sciences, Korean manufacture) – 0.01% THIM-50μg/dose, DT (Biomed, Krakow) – 50μg/dose, Td (Biomed, Krakow) – 50μg/dose, DTP (Biomed, Krakow) – 50μg/dose, D,d (Biomed, Krakow) – 50μg/dose, TT (Biomed, Krakow) – 50μg/dose [4, 55]. The frequency of observed reactions and complications depend on the general condition, especially neurological, of the child, the age, immunological resistance status as well as family and genetic load. In the literature, neurological symptoms are usually connected with the pertussis component of the vaccines, including: cerebral cry, according to Cody, occurs in 1:1000 of vaccinated subjects; seizures – mild, feverish – triggered by the pertussis endotoxin, in 10% of vaccinated subjects the convulsions occur without elevated body temperature, and severe seizures occur according to Waller et al. in 1 in 106,000 children [25]. In serious complications, such as encephalitis (about 2.9/10,000,00 of those vaccinated with DTP), encephalopathy (1:140,000 – 1:300,000 of the vaccinated), which may result in mental retardation, recurrent seizures, epilepsy – particularly myoclonic and Lennox-Gastaut Syndrome, changes in the central nervous system comparable to those which occur in the course of meningitis and encephalitis were reported. In the early stages, perivascular lymphocytic infiltration and demyelination outbreaks were observed, then myelin atrophy with intact neuron axial fiber, degenerated microglia and macrophage cells. Some experimental studies suggest the pertussis toxin, which through the membrane receptors causes inhibitory neurotransmitter dysfunction and induces activity of excitatory neurotransmitters [56, 57]. In 2010, a case of a 6-month-old previously healthy boy admitted to hospital on day 6 after vaccination with DTwP (whole cell) was described. The child was in a coma, hypotonia, with focal clonic seizures. MRI of the central nervous system using proton spectroscopy revealed acute necrotizing encephalopathy [58]. Previously, epileptic seizures in children with asymptomatic CMV infection which occurred after vaccination with DTwP and OPV had also been described. In the case of hepatitis C virus (HCV) infection, DTaP (acellular) and IPV (inactivated) vaccinations are recommended [59]. As stated in the Polish literature, acellular vaccines are much better tolerated than whole cell – the risk of fever after the first dose is reduced by over 99%, the risk of hypotonic-hyporesponsive episodes by 56%, similar to seizures, and the risk of inconsolable crying after the first dose is reduced by 87% [4]. According to the current vaccination schedule in Poland, infants receive the first three doses of DTwP in the first 6-8 weeks of life every 6-8 weeks, the 4th dose in the 16th-18th month of life, and a DTaP booster at 6 years of age. Given the often reported neurological complications after whole-cell pertussis (DTwP, DTP) vaccine, most developed countries – European and the US – have introduced changes in their immunization schedules and the safer acellular (DTaP) vaccines are administered to children. Of these countries, the only exceptions are: Bulgaria, Malta and Poland. In Poland, the safe vaccine is paid in full.

Other neurological complications associated with the administered vaccination are listed, among others, as follows:

  • multiple sclerosis after hepatitis B vaccine [60],
  • Guillain-Barre syndrome – after vaccination against influenza, hepatitis, meningitis C, polio and HPV vaccines [61-65],
  • transverse myelitis as a result of vaccination against cholera, typhoid, polio, and influenza,
  • flaccid paralysis, meningitis, encephalitis, convulsions and facial palsy after live polio vaccine [65, 66],
  • rapid progression of retinopathy in premature infants after BCG vaccination [67].

Monitoring In the case of AEFI, the obligation of notification was described in article 21 of the Preventing and fighting infections and infectious diseases in humans Act. According to the Act, a physician who recognizes or suspects the occurrence of AEFI is required, within 24 hours after concluding the suspicion, to notify the State Sanitary Inspector of the suspected case [3]. In order for that to be possible, the child’s guardian must also be accurately informed about the adverse symptoms following vaccination that may occur, then report the problem to the doctor or nurse who will take further steps.

There was an attempt to trace the actual scale of the adverse events following vaccination reported by nurses and doctors. Prog Health Sci 2012, Vol 2 , No1 Neurologic adverse events vaccination 136  The monitoring system was introduced in Poland in 1996 and is based on the WHO recommendations. In the Zieliński study, the number of AEFI reported in 1996-2000 from different provinces was analyzed and clear differences regarding the frequency of recorded entries were found. As the authors write, “they met astonishing examples of ignorance of the medical staff, including specialists, in their duty to report the AEFI” in their epidemiological practice [68]. On the other hand, there is no real possibility of laboratory tests to confirm a causal relationship between the clinical picture and the used vaccine. For example, only a few research laboratories in Poland, of the highest reference level, posses the microbiological methods for distinguishing mycobacteria from the BCG vaccine from other species of the Mycobacterium tuberculosis strain [69]. There are also no reports in the literature (except those listed above) of research work in immunology in the context of reactions following vaccination. It should also be noted that in more developed countries, there is little incentive for doing appropriate follow-up and laboratory tests on individuals who suffered serious adverse reactions following vaccinations [70]. The reason for such oversight is likely due to the fact that historically, vaccines have not been viewed as inherently toxic by the regulatory agencies [68] The resulting lack of evidence of causality between vaccinations and serious adverse outcomes has thus been filled with an assumption that vaccines are safe [71]. Natural history of infectious diseases/ immunizations Based on statistics from the Federal Statistics Office in Wiesbaden, Buchwald published a paper containing long-term observations of morbidity and mortality from infectious diseases. It is interesting that in recent decades a decrease of infectious diseases was generally reported, which took place before the introduction of inoculations against these diseases. According to a 2002 report from Lancet Infectious Diseases [72] ―the weight of evidence collectively suggests that personal and environmental hygiene reduces the spread of infection‖ and ―Thus results from this review demonstrate that there is a continued, measurable, positive effect of personal and community hygiene on infectious‖. The same report showed that the crude death rate from infectious diseases decreased to nearly negligible levels long before introduction of universal vaccination practices. Currently, the developed countries introduce increasingly complex vaccination schedules. Forty years ago, children were immunized against five diseases (diphtheria, tetanus, pertussis, polio, smallpox), today this number has increased to eleven. At the same time, as mentioned previously, repeatedly administered multi-antigen vaccines are recommended. Doctors and researchers point to the worsening state of health of the child population since the 1960s, which coincided with increasingly introduced vaccinations. Allergic diseases, including asthma, autoimmune diseases, diabetes and many neurological dysfunctions – difficulty in learning, ADD (attention deficit disorder), ADHD (attention deficit hyperactivity disorder), seizures, and autism – are chronic conditions, to which attention has been brought [73]. Proposals for modification of the vaccination schedule European countries have different models of vaccination that have been modified in recent decades. In Scandinavian countries, which have the lowest infant mortality, vaccinations are voluntary and infants receive their first vaccination at 3 months of age. In the first year of life, they receive 9 recommended vaccinations, and at 18 months – MMR. The acellular pertussis vaccine (DTaP) is used, as well as IPV. BCG and Hepatitis B vaccines are administered to children from high risk groups. Similar vaccination schedules exist in other European countries, where the vaccination of neonates was abandoned and a ban on the use of thimerosal in vaccines was introduced [4, 74]. Note also that Scandinavian countries have the lowest rates of autism compared to other developed countries in which children are vaccinated much earlier and with greater number of vaccines [49]. Professor Majewska – a neurobiologist, Director of the Marie Curie Chairs Program at the Department of Pharmacology and Physiology of the Nervous System in Warsaw – together with pediatricians, drafted a proposal for changes to the vaccination program in Poland, which is based on an analysis of programs in other European Union countries. The propositions are as follows:

1. Eliminate thimerosal from all vaccines.

2. Discontinue the immunization of infants with the hepatitis B vaccine (vaccinate only newborns at high risk, i.e. of infected mothers).

3. Discontinue BCG vaccination of neonates (use only in regions where the percentage of TB patients is over 40 per 100 thousand).

4. Begin vaccination from 4 months old in the remaining group of children.

5. Discontinue the whole cell pertussis vaccine.

6. Give a maximum of three types of vaccines in one day.

7. Discontinue the administration of live virus vaccines or give them one at a time at safe intervals.

8. Make monovalent vaccines accessible.

9. Commitment of the doctor administering the vaccine to conduct a preliminary interview with the parents about allergies, asthma and other autoimmune diseases and postvaccinal complications in family members, allowing them to predict whether a given child may experience severe postvaccinal reactions. Such a child should have an individual, very careful vaccination program developed.

10. Monitor the health status of children after vaccination in order to notice life- or healththreatening conditions in time.

11. Create a national program for compulsory registration of postvaccinal complications and deaths. These data should be reported to the WHO and information about complications should be provided in the child’s health record book [51]. Prog Health Sci 2012, Vol 2 , No1 Neurologic adverse events vaccination 138

CONCLUSIONS

Despite the assurances of the necessity and safety of vaccinations, there are more and more questions and doubts, which both physicians and parents are waiting to be clarified. This paper describes several aspects of the immunization program of children. It includes:

  • the physiological development of the immune system,
  • the immunization schedule adopted in Poland in comparison with other countries,
  • adverse reactions and complications following vaccination described in scientific publications,
  • the natural course of infectious diseases in conjunction with the vaccination programs implemented
  • and the problem of reporting adverse reactions following vaccination by medical personnel and parents.

The proposal for changes in vaccination in Poland cited at the end of this paper is, according to the authors, part of the answer to the concerns and doubts. A second part would be extensive neuroimmunological research confirming or excluding the relationship of vaccines with the reported adverse events (early, late/long-term) and chronic diseases whose upward trend has been observed in recent decades in children. It seems that it would be worthwhile to apply the precautionary principle – the ethical principle (from 1988) according to which if there is a probable, although poorly known, risk of adverse effects of new technology, it is better not to implement it rather than risk uncertain but potentially very harmful consequences.

ACKNOWLEDGMENTS

We are grateful to Mrs. Ursula HumienikDworakowska for the translation of this article.

Conflicts of interest

We declare that we have no conflicts of interest.

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