Yates v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 14-560V

(Filed: April 16, 2020)

* * * * * * * * * * * * *

JEAN YATES, individually and as a * To Be Published

representative of the late *

ROBERT YATES, *

*

Petitioner, * Denial of Entitlement; Meningococcal

* Conjugate (“Menactra”) Vaccine;

v. * Lymphocytic Myocarditis; Death

*

SECRETARY OF HEALTH *

AND HUMAN SERVICES, *

*

Respondent. *

*

* * * * * * * * * * * * *

Patricia Finn, Esq., Patricia Finn, P.C., Piermont, NY, for petitioner.

Voris Johnson, Esq., U.S. Department of Justice, Washington, DC, for respondent.

DECISION1

Roth, Special Master:

On June 30, 2014, Jean Yates (“Ms. Yates,” or “petitioner”) filed a petition as

representative for the estate of her deceased son, Robert Yates (“Robert”), for compensation under

the National Vaccine Injury Compensation Program, 42 U.S.C. §300aa-10, et seq.2 (the “Vaccine

Act” or “Program”). The petition alleged that “[t]he death of Mr. Yates ‘was caused in fact’” by a

meningococcal conjugate (“Menactra”) vaccination he received two days before on July 28, 2011.

1

This Decision has been designated “to be published,” which means I am directing it to be posted on the

Court of Federal Claims’ website, in accordance with the E-Government Act of 2002, Pub. L. No. 107-347,

116 Stat. 2899, 2913 (codified as amended at 44 U.S.C. § 3501 note (2006)). This means the Decision will

be available to anyone with access to the internet. However, the parties may object to the Decision’s

inclusion of certain kinds of confidential information. Specifically, under Vaccine Rule 18(b), each party

has fourteen days within which to request redaction “of any information furnished by that party: (1) that is

a trade secret or commercial or financial in substance and is privileged or confidential; or (2) that includes

medical files or similar files, the disclosure of which would constitute a clearly unwarranted invasion of

privacy.” Vaccine Rule 18(b). Otherwise, the whole Decision will be available to the public. Id.

2

National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755. Hereinafter, for ease

of citation, all “§” references to the Vaccine Act will be to the pertinent subparagraph of 42 U.S.C. § 300aa

(2012).

Petition at 1, ECF No. 1.3

An entitlement hearing was conducted on July 27 and 28, 2017, in Washington, DC. Ms.

Yates has suffered a tremendous loss due to the death of her son and the deepest sympathies are

extended to her and her family. However, following careful review and analysis of all of the

documentary evidence and testimony submitted in this case by both petitioner and respondent and

in accordance with the applicable legal standards, I find that petitioner has not proffered sufficient

evidence to demonstrate that the Menactra vaccination that Robert received on July 27, 2012 was

the cause in fact or contributed to his death. Accordingly, I find that petitioner is not entitled to

compensation.

I. Issues to be Determined

The issues to be determined are whether preponderant evidence exists to establish a reliable

medical theory, a logical sequence of cause and effect, and a medically-appropriate temporal

relationship between vaccination and Robert’s death to prove that the Menactra vaccine

administered on July 27, 2012 caused and/or contributed to Robert’s myocarditis and death. See

Jt. Sub. at 1-2.

A key fact in dispute is whether Robert suffered from lymphocytic myocarditis or

eosinophilic myocarditis.

The parties agree that the medical records are “generally accurate.” Jt. Sub. at 1. The parties

agree that only the autopsy report suggested that Robert had a seizure on the day that he died and

that “[a]ll other contemporaneous records…do not establish that Robert actually had a seizure on

the day he died.” Id.

II. Procedural History

The petition was filed on June 30, 2014 and assigned to Special Master Dorsey. ECF Nos.

1-2. Petitioner filed medical records through November of 2014. See Petitioner’s Exhibits (“Pet.

Ex.”) 1-3, ECF No. 6; Pet. Ex. 4-5, ECF No. 10; Statement of Completion, ECF No. 11.

On February 5, 2015, respondent filed his Rule 4(c) Report (“Resp. Rpt.”) advising against

compensation in this matter. ECF No. 14. Respondent noted that the Petition did not state the

correct date of vaccination. Resp. Rpt. at 1 n.1. Respondent further noted that Robert received his

second Menactra vaccination on July 27, 2012 and requested “that petitioner file all medical

records documenting [Robert’s] receipt of the first Menactra vaccine.” Id. at 3 n.3. Respondent

noted that, on autopsy, “Robert had a mildly dilated right heart ventricle and mild hypertrophy of

his left heart ventricle” and his “cause of death was listed as ‘microlymphocytic myocarditis,

natural.’” Id. at 4.

During a status conference on February 24, 2015, petitioner advised that she would be

3

The Petition provided an incorrect date of vaccination; the contemporaneous medical records reflect that

Robert received the allegedly causal Menactra vaccination on July 27, 2012, three days prior to his death.

See Pet. Ex. 1 at 54.

2

filing the report of Dr. Chang, a cardiologist. Scheduling Order at 1, ECF No. 15. Special Master

Dorsey noted that this matter involves a complex diagnosis, on which Dr. Chang may be well

equipped to opine; however, should that not be the case, petitioner should consider obtaining an

additional report from an infectious disease specialist or an immunologist. Id. The special master

requested that all experts review and opine on the medical examiner’s report and resulting

conclusions. Id. She also raised the conflicting dates in the record for Robert’s receipt of the

Menactra vaccine. Id. at 1-2. Petitioner’s counsel confirmed that the allegedly causal vaccine was

administered on July 27, 2012, and that the first Menactra vaccine Robert received was given on

August 25, 2005. Id. at 2.

On May 26, 2015, Petitioner filed an expert report from Dr. Anthony Chang along with Dr.

Chang’s curriculum vitae (“CV”). Pet. Ex. 6-7, ECF No. 20. On June 3, 2015, Petitioner filed

supporting literature and an updated CV for Dr. Chang. Pet. Ex. 8, ECF No. 21; Pet. Ex. 9, ECF

No. 22. On July 30, 2015, petitioner filed her Affidavit. Pet. Ex. 10, ECF No. 24.

On August 14, 2015, respondent filed a Motion for Extension of Time within which to file

his expert report and requesting that petitioner provide the actual autopsy slides for respondent’s

expert pathologist to review; this motion was granted. ECF Nos. 25-26. On September 18, 2015,

petitioner filed a status report advising of her efforts to secure the autopsy slides and the expected

date of receipt. ECF No. 27. On October 2, 2015, petitioner filed a status report advising that the

autopsy films were forwarded directly by Westchester County Medical Examiner’s Office to

respondent’s counsel. ECF No. 29.

This matter was reassigned to me on October 22, 2015. ECF Nos. 30-31. On November

13, 2015, respondent filed the reports and CVs of Scott Yeager, M.D., a cardiologist, and Rebecca

Folkerth, M.D., a pathologist. Respondent’s Exhibits (“Resp. Ex.”) A-D. ECF No. 33. On

November 19, 2015, respondent filed medical literature via CD. Resp. Ex. A, Tabs 1-13, Resp. Ex.

C, Tabs 1-4, ECF No. 34.

During a status conference on December 4, 2015, petitioner’s counsel advised that she

intended to file a report from a pathologist and a supplemental report from Dr. Chang. Scheduling

Order at 1, ECF No. 35. Petitioner filed two Motions for Extensions of Time thereafter to file her

expert reports, which were granted. ECF Nos. 36-37. On April 20, 2016, petitioner filed the

supplemental expert report of Dr. Chang, an expert report and CV from Dr. Laurel Waters, and

supporting medical literature. Pet. Ex. 11-17, ECF No. 38.

During a status conference on June 9, 2016, respondent’s counsel advised that he would

not be filing any additional expert reports. ECF No. 39. On July 7, 2016, the parties filed a joint

status report suggesting hearing dates. ECF No. 40. A two-day entitlement hearing was set for July

27-28, 2017. See Prehearing Order, ECF No. 41.

On August 3, 2016, respondent filed a supplemental expert report from Dr. Yeager and

supporting medical literature. Resp. Ex. E, Resp. Ex. E, Tab 1, ECF No. 43.

The parties filed their prehearing submissions. Pet. Brief, ECF No. 44; Resp. Brief, ECF

No. 45; Jt. Sub., ECF No. 47; Pet. Reply Brief, ECF No. 49.

3

On July 26, 2017, the day prior to the hearing, chambers reached out to counsel regarding

the results of a Luminex Virus Panel Assay believed to have been performed during Robert’s

autopsy. In her report, Dr. Folkerth wrote, “Virology: No detection of Influenza A, A/H1, A/H3,

B, RSV A, RSV B, Parainfluenza 1, 2, and 3, Human Metapneumovirus, Rhinovirus, or

Adenovirus (by Luminex Virus Panel Assay).” Resp. Ex. C at 3. In her supplemental report,

petitioner’s expert, Dr. Waters wrote, “Virology produced a negative Luminex Virus Panel Assay,

specifically Influenza A, A/H1, A/H3, B; RSV A & B; Parainfluenza 1, 2 & 3; Human

Metapneumovirus; Rhinovirus and Adenovirus. Bacteriology showed negative cultures for blood

and an unspecified body fluid.” Pet. Ex. 13 at 5. Dr. Waters concluded that the viral assay showed

no viral infection. Id. Despite an exhaustive review of the medical records, the actual test results

for the Luminex Virus Panel Assay could not be located. Respondent’s counsel responded via

email that he could not locate the results either. There was no response from petitioner’s counsel.

Early in the hearing, the issue of the Luminex Virus Panel Assay referenced by both Dr.

Waters and Dr. Folkerth was raised. Tr. 41-44. At that time, petitioner’s counsel advised that she

was going to wait for her cross-examination of Dr. Folkerth before advising the Court that,

following my inquiry the previous day, she reached out to the medical examiner’s office and was

advised that a Luminex Virus Panel Assay was not performed. Tr. 105. Counsel did not think it

necessary to advise the Court of her findings prior to hearing.

At that point, Dr. Folkerth advised that she was uncertain of where that information came

from, conceding that no test results could be found in the medical records for this case, and her

reference to it was clearly a mistake. Tr. 101, 106. She added that assay testing is standard in

connection with autopsies but, having written her report over two years ago, she could not recall

where the information came from, again admitting her mistake. Tr. 101. Dr. Waters admitted to

having taken the information directly from Dr. Folkerth’s report when writing her own report,

never looking for the actual report to verify the information. Tr. 41-42.

Petitioner’s counsel then moved to have Dr. Folkerth’s report and testimony barred in

totality. Tr. 102-03. Respondent’s counsel offered to have any reference to the assay excluded

completely from the case. However, petitioner’s counsel continued to argue, refusing to have it

excluded and demanding to know where Dr. Folkerth got the information. Tr. 103-04. I advised

petitioner’s counsel that since she received confirmation that the assay was never performed,

neither side would get the benefit or detriment from the absence of results. Tr. 104. Petitioner’s

counsel continued to demand that Dr. Folkerth explain where the information came from, arguing

that this mistake meant Dr. Folkerth had made other mistakes in her report and her opinions should

be barred. Tr. 106. Despite discussion, petitioner’s counsel refused to appreciate that, while Dr.

Folkerth included the mistaken results in her statement of the autopsy findings, Dr. Waters not

only included the information in her report without ever looking for or seeing the report, but more

importantly relied on the results of a test she never actually reviewed in reaching her conclusion

that the assay testing was negative for viral infection therefore the Menactra vaccine Robert

received was the cause of his myocarditis and death.

I asked Dr. Folkerth if the assay testing could still be done on the pathology slides to

determine if an infection was present. Tr. 142. She advised that, if the slides were sent to the CDC,

the testing could be performed. Tr. 142. An Order was issued after the hearing for the slides to be

4

sent to the CDC for testing. See Scheduling Order, ECF No. 52.

On April 2, 2018, petitioner filed a status report stating she had been advised by the

Westchester County Medical Examiner that the testing could not be done with the slides that still

existed; the tissue slides that would be required for such testing were destroyed six months after

Robert’s death. Status Report, ECF No. 67. Petitioner’s counsel again insisted that Dr. Folkerth’s

opinions were based on the nonexistent assay results and should be barred. Id. at 1-2. Petitioner

requested a status conference to discuss filing a Motion to Strike Dr. Folkerth’s expert report and

testimony. Id. at 2.

The requested status conference was held on May 23, 2018 to again discuss the issue of

the Luminex Virus Panel Assay referenced by Dr. Folkerth and relied on by Dr. Waters.

Scheduling Order at 2, ECF No. 68. I again advised that Dr. Folkerth only documented the results

of the assay in her case summary but did not base her opinion in this case on those results. Id.,

citing Resp. Ex. C at 5. On the other hand, petitioner’s expert, Dr. Waters, not only relied on Dr.

Folkerth’s case summary without ever looking at the medical record herself to confirm whether an

assay had been performed, but relied on the “results” of the assay to conclude that, because the

viral assay showed no viral infection, the vaccine was the cause of the lymphocytic myocarditis

and ultimately, Robert’s death. Id., citing Pet. Ex. 13 at 5, 7.

I advised counsel that if I were to strike Dr. Folkerth’s expert report and testimony, I would

also strike Dr. Waters’ report and testimony since Dr. Waters relied on the results of the assay in

formulating her opinion in this matter. Scheduling Order at 2, ECF No. 68. Finally, I advised

counsel that, since the assay was never performed and there was no proof of viral infection at the

time of petitioner’s Menactra vaccine, the issue is moot, with no benefit or detriment to either side.

Id. In fact, the absence of the assay was a benefit to petitioner, since we did not have definitive

proof that petitioner suffered from an illness that was the cause of his lymphocytic myocarditis.

Id. I advised petitioner’s counsel that I could not stop her from filing a Motion to Strike Dr.

Folkerth’s opinions and testimony, but the foregoing would be my opinion on such a motion. Id.

Petitioner did not file that motion.

Counsel were asked if they wanted to file post-hearing briefs in this matter. Petitioner’s

counsel stated that she would like the opportunity to file a post-trial brief. Scheduling Order at 2,

ECF No. 68. Petitioner was ordered to file her post-hearing brief by August 20, 2018; respondent’s

post-hearing brief was due 60 days thereafter. Id.

Following three extensions of time, petitioner filed her post-hearing brief on November 28,

2018. See Motion for Extension of Time, ECF No. 69; Non-PDF Order, issued Aug. 16, 2018;

Motion for Extension of Time, ECF No. 70; Non-PDF Order, issued Oct. 19, 2018; Motion for

Extension of Time, ECF No. 71; Non-PDF Order, issued Nov. 28, 2018; Pet. Post-Hearing Brief,

ECF No. 72. Petitioner’s post-hearing brief was missing citations to both the transcript and the

medical literature; the caption was also incorrect. Scheduling Order at 1, ECF No. 73. Petitioner

was ordered to file a Motion to Strike her post-hearing brief and refile a corrected copy. Id.

On December 3, 2018, petitioner filed a Motion to Strike her post-hearing brief; petitioner’s

Motion contained an incorrect caption. ECF No. 74. My chambers contacted petitioner via email

5

and requested that she move to strike and refile her Motion to Strike with the correct caption. See

Order at 1, ECF No. 79. On December 4, 2018, petitioner filed a Motion to Strike both her post-

hearing brief and her original Motion to Strike. ECF No. 75. An Order was issued granting this

motion on December 6, 2018. ECF No. 79.

On December 5, 2018, petitioner filed a corrected copy of her post-hearing brief, an

additional article of medical literature, the Menactra package insert, and an excerpt from a textbook

discussing meningococcal disease. Pet. Ex. 25, ECF No. 76; Pet. Post-Hearing Brief, ECF No. 77;

Pet. Ex. 26-27, ECF No. 78.

Respondent filed his post-hearing brief on January 29, 2019. Resp. Post-Hearing Brief,

ECF No. 80. On March 5, 2019, petitioner filed a reply to respondent’s post-hearing brief and an

additional article of medical literature. Pet. Post-Hearing Reply, ECF No. 82; Pet. Ex. 28, ECF No.

83. Petitioner’s reply was filed using the incorrect CM/ECF event, and she was instructed to file a

Motion to Strike her reply brief. Later that day, petitioner filed a Motion to Strike, which was

granted. ECF Nos. 84, 86. Petitioner then filed her reply brief as a “Response to Reply” brief. See

ECF No. 85. Petitioner was advised that she had again filed her brief using the wrong CM/ECF

event. See Order at 1, ECF No. 91. Petitioner was also informed that she was not authorized to file

medical literature with her reply brief, and she would need to either obtain respondent’s consent

to file additional medical literature or file a Motion for Leave to Submit Additional Literature. See

id. Petitioner was instructed to file a Motion to Strike both her reply brief and article of medical

literature. See id. Petitioner filed this Motion on March 5, 2019; it was granted on March 12, 2019.

ECF Nos. 87, 91.

On March 6, 2019, petitioner filed her reply brief as a “Notice.” ECF No. 88. She filed a

“Motion to Leave to File Attached Medical Literature Out of Time” on March 8, 2019. ECF No.

89. Petitioner submitted that the attached article, “Yamamoto et al.,” was published in October of

2018 and was relevant to petitioner’s claim because it observed lymphocytes in a case of

eosinophilic myocarditis following a vaccine. Id. at 1. Respondent filed a response to this Motion

on March 11, 2019, opposing petitioner’s Motion. ECF No. 90. Respondent submitted that the

article was irrelevant because it discussed eosinophilic myocarditis rather than lymphocytic

myocarditis. Id. at 1. Respondent requested that, in the event that the special master granted

petitioner’s motion, respondent be allowed to file a written response from his expert addressing

the article. Id. at 3.

On March 12, 2019, an Order was issued granting petitioner’s motion based on Federal

Circuit precedent requiring special masters to consider all relevant medical and scientific evidence

of record. See Scheduling Order at 2, ECF No. 92 (citing Moriarty ex rel. Moriarty v. Sec’y of

Health & Human Servs., 844 F.3d 1322, 1330 (Fed. Cir. 2016)).

Petitioner filed the Yamamoto article on March 18, 2019. Pet. Ex. 28, ECF No. 93.

Respondent filed a supplemental report from Dr. Folkerth on April 9, 2019 addressing the article.

Resp. Ex. F, ECF No. 94. An Order closing the record was issued on May 22, 2019. ECF No. 95.

This matter is now ripe for decision.

6

III. The Factual Record

A. Robert’s Medical History Prior to the Menactra Vaccine

Robert was born on January 9, 1994. Pet. Ex. 1 at 10. His medical history included

pervasive developmental disorder, “moderate to severe autism,” and epilepsy. Id. at 10, 47; Pet.

Ex. 2.2 at 6, 8. Prior to his receipt of the allegedly causal Menactra vaccine, Robert received all

routine childhood vaccinations without event. Pet. Ex. 1 at 67-68.

The earliest record filed was April 7, 2009. Robert was presented to Dr. Selman at

Blythedale Children’s Hospital for neurologic evaluation. Pet. Ex. 5 at 5-6. He was a 15-year-old

with known pervasive developmental disorder and familial history of same. Id. He did not have

seizures. Id. He attended a special needs program, where he was learning keyboarding. Id. He

could spell and understand spelled words, but his reading level was unknown. He had tantrums at

school. Id. He exhibited several stereotypical behaviors, including shaking his hands, jumping,

yelling, and rocking. Id. at 6. He could follow commands such as “give five” or “hold [your] arms

up.” Id. He took five mg of Valium4 twice per day. Id. Dr. Selman asked for Robert’s recent IEP,

for a detailed tantrum diary to be kept, and for the school to provide the techniques being used to

manage his physical outbursts. Id. Dr. Selman recommended re-evaluation during the summer of

2009. Id.

The next record was a phone call from Robert’s father to the pediatrician, Dr. Barsh, on

January 1, 2011. Robert now had a seizure disorder5 and a refill of clonazepam6 was needed. Pet.

Ex. 1 at 8.

On February 11, 2011, emergency medical services were called to the Yates’ home. Pet.

Ex. 2.2 at 4. Upon arrival, EMS personnel found Robert on the stairs of his home, “somewhat

subdued” and “moderately responsive.” Id. He had reportedly had a seizure on the school bus. Id.

EMS personnel deemed the home unsafe7 and notified Child Protective Services (“CPS”). Id.

Robert was transported via ambulance to Northern Westchester Hospital Center (“NWHC”)

Emergency Room. Id. at 6.

Dr. Bedi, the ER physician at NWHC, noted that Robert had a seizure disorder with a

4

Valium is the brand name for diazepam, an anti-anxiety agent used to treat anxiety disorders; it can also

be used as a skeletal muscle relaxant or anticonvulsant. Valium, DORLAND’S ILLUSTRATED MEDICAL

DICTIONARY 2020 (32nd ed. 2012) [hereinafter “DORLAND’S”]; diazepam, id. at 512.

5

There is a gap in the medical records between April 7, 2009 and January 1, 2011; accordingly, there is no

indication of when Robert began having seizures.

6

Clonazepam is an anticonvulsant used to treat atonic and myoclonic seizures. Clonazepam, DORLAND’S

at 373.

7

EMS personnel wrote, “Debris all over house w/ only narrow passageway throughout house. 2 other sons

living in house – one witnessed living in “caged-off” area – no furniture/clothing.” Pet. Ex. 2.2 at 4.

7

history of breakthrough seizures, for which he took Klonopin,8 Keppra,9 and Valium. Pet. Ex. 1 at

10. That day, Robert had a “brief, 10-second seizure” “while going to the school bus.” Id. at 9, 10;

Pet. Ex. 2 at 57. His parents gave him Klonopin, and the seizure stopped. Id. at 10. The bus driver

had called the paramedics. Id.

Upon examination, Robert had redness, swelling, and healing bite marks on both wrists.

Pet. Ex. 2 at 71. Blood work showed high glucose, sodium, hemoglobin, hematocrit,10

eosinophils11 at 7.2 (on a 0.0 to 6.0 scale), and low alkaline phosphatase,12 MPV,13 and

lymphocytes.14 Pet. Ex. 2.2 at 19, 21. Robert was given a fluid bolus;15 follow-up with the

neurologist was recommended. Pet. Ex. 1 at 9, 10. CPS agreed to allow Robert’s parents to take

him to a hotel while the home was being fixed. Id.; Pet. Ex. 2 at 57.

On March 28, 2011, Robert was presented to Dr. Barsh for several days of cough and fever.

Pet. Ex. 1 at 13. He was taking 150 mg of Keppra twice per day and two 5 mg tablets of Valium

twice per day. Id. He used Klonopin for seizures as needed. Id. Dr. Barsh prescribed 500 mg of

Zithromax16 daily for five days and recommended a follow-up in ten days if Robert was not better.

Id.

8

Klonopin is the brand name for clonazepam. Klonopin, DORLAND’S at 989.

9

Keppra is the brand name for levetiracetam, an anticonvulsant medication used in the treatment of partial

and myoclonic seizures and idiopathic generalized epilepsy. Keppra, DORLAND’S at 978; levetiracetam, id.

at 1031.

10

“Hematocrit” is an indirect measurement of red blood cell numbers and volume. It is used as a rapid

measurement of red blood cell count. See Mosby’s Manual of Diagnostic and Laboratory Tests 249 (Pagana

eds., 6th ed. 2018) [hereinafter “Mosby’s”].

11

An eosinophil is a type of white blood cell that is involved in allergic reactions. Mosby’s at 468.

Eosinophils do not respond to bacterial or viral infections. Id. Increased eosinophil levels can indicate

parasitic infection, allergic reaction, eczema, leukemia, or autoimmune disease. Id. at 473.

12

Alkaline phosphatase (“ALP”) is an enzyme concentrated in the liver and bones. Mosby’s at 43-44. ALP

levels are used to detect and monitor diseases of the liver or bone. Id. Low ALP levels can indicate low

phosphate levels, malnutrition, milk-alkali syndrome, pernicious anemia, or vitamin C deficiency. Id.

13

Mean Platelet Volume (“MPV”) is a measure of the volume of platelets which varies with total platelet

production. MPV is used to evaluate platelet disorders, including thrombocytopenia. Mosby’s at 367. Low

MPV levels can indicate aplastic anemia, chemotherapy-induced myelosuppression, or Wiskott-Aldrich

syndrome. Id. at 368.

14

A lymphocyte is a type of white blood cell that fights chronic bacterial infection and acute viral infections.

Mosby’s at 468-69. There are two types of lymphocytes, T-cells, which are involved in cellular-type

immune reactions, and B-cells, which participate in antibody production. Id. at 468.

15

A bolus is a single, relatively large quantity of a fluid or dose of a drug injected intravenously. Bolus,

STEDMAN’S MEDICAL DICTIONARY 111520, accessed via WESTLAW EDGE (last visited Apr. 10, 2020).

16

Zithromax is the brand name for azithromycin, an antibiotic used to treat mild to moderate bacterial

infections. Zithromax, DORLAND’S at 2092; azithromycin, id. at 187.

8

On July 6, 2011, Robert presented to Dr. Sweeney for neurological follow-up. Pet. Ex. 1

at 15. His father reported that Robert had five seizures in the past month which lasted between

three and five minutes. Id. During the most recent seizure, the convulsions caused Robert to hit his

face on an end table and bleed. Id. He was given clonazepam melt-away tablets on his tongue,

which helped. Id. It was hard to tell if he was incontinent as he was not toilet trained. Id. Robert’s

father reported that weather changes and heat brought on seizures. Id. He further reported that

Robert had not been sleeping well due to changes in the home; he had a new bedroom, a new bed,

and a new computer. Id. He was taking 5 mg of Valium four times per day, one mg of clonazepam

at bedtime, and Keppra twice daily. Id. He was minimally interactive but awake, alert, and

cooperative. Id. The plan was to increase Keppra to 2000 mg twice per day. Id. at 16. Blood work

showed elevated eGFR17 and SGPT (ALT).18 Id. at 18. Eosinophils were normal, at 4.3 on a scale

of 0.0 to 6.0. Id. at 17. A1C19 and glucose levels were also normal. Id. at 14.

One week later, on July 13, 2011, Robert was presented to Dr. Barsh for an upper

respiratory infection. Pet. Ex. 1 at 19. His mother reported drooping of the right eye, “almost like

a Bell’s palsy,” that morning. Id. There was no history of tick bites or rashes. Examination was

normal. Id. Dr. Barsh wrote, “I am glad to say Robert does not have a Bell’s palsy. We are going

to do a Lyme titer. No treatment is needed for his upper respiratory infection. Id. The Lyme Titer-

Western blot came back EIA positive, but the IgM was negative with no bands, which according

to the criteria was considered a negative test. Id. at 20-22.

Robert returned to Dr. Barsh one week later, on July 20, 2011, for his 17-year-old checkup.

Pet. Ex. 1 at 25. He attended a special education program at the high school to learn computers.

Id. He slept better when he had school the next day but would stay up late on other nights. Id. He

enjoyed electronic games, walking, and staying busy outside. Id. He was taking 2000 mg of Keppra

twice a day and Klonopin as needed. His A1C had been 5.5 but was improving with diet. Id. He

was deemed a healthy 17-year-old with autism spectrum disorder. Id. Follow up with neurology

for seizure disorder was advised. Id.

On July 22, 2011, Dr. Sweeney’s neurology practice noted that Robert had a seizure the

day before. His Keppra was increased to 2500 mg in the morning and 2000 mg at night. Pet. Ex. 1

at 26.

17

eGFR stands for “estimated glomerular filtration rate.” It is a test that measures the level of kidney

function. Estimated Glomerular Filtration Rate (eGFR), NATIONAL KIDNEY FOUNDATION,

https://www.kidney.org/atoz/content/gfr (last visited Mar. 23, 2020).

18

Alanine aminotransferase (“ALT”), also known as serum glutamic-pyruvic transaminase (“SGPT”), is an

enzyme found predominantly in the liver. Mosby’s at 36. ALT levels are used to identify liver diseases.

Mildly increased ALT levels can indicate pancreatitis, myocardial infection, infectious mononucleosis, or

shock. Id. at 37. Moderately increased ALT levels can indicate cirrhosis, severe burns, muscle trauma, liver

tumor, obstructive jaundice, cholestasis, or presence of drugs toxic to the liver. Id. Significantly increased

ALT levels can indicate hepatitis, liver necrosis, or ischemia of the liver. Id.

19

The test for glycosylated hemoglobin, colloquially referred to as “A1C,” is used to diagnose and monitor

diabetes treatment. It provides an accurate long-term index of the patient’s average blood glucose level.

Mosby’s at 238.

9

On September 23, 2011, Robert was presented to Dr. Barsh with hematuria. Pet. Ex. 1 at

28. Upon exam, he did not have bellyache, backache, or fever, and had no signs of kidney stones.

Id. Prescriptions for Keppra, Valium, and clonazepam were written and given to Robert’s father.

Id.

On November 2, 2011, prescriptions for Keppra and clonazepam rapid dissolve tabs were

given to Robert’s father. Id.

On November 18, 2011, Robert was presented to Dr. Barsh for a contusion of the right

foot. Pet. Ex. 1 at 30. An x-ray showed no fracture. Id. at 30-31.

On December 28, 2011, Robert was presented to Dr. Ratner at Mount Kisco Medical Group

for vomiting, nasal congestion, and being “a bit out of sorts.” Pet. Ex. 1 at 32. His dad was

concerned for strep throat; he also had a cut on his foot. Id. A rapid strep test was negative. Id. at

32-33. Dr. Ratner removed a splinter from Robert’s foot and recommended that he soak his foot

four times per day. Id. at 32.

On January 16, 2012, Robert was presented to Dr. Barsh for persistent cough and ear pain

keeping him up at night for two weeks. Pet. Ex. 1 at 34. He had two breakthrough seizures which

his father reported were usual when he had an infection Id. Chest and cardiac examination were

normal. Id. There was no fever. Id. Amoxicillin for ten days was prescribed for a possible sinus

infection. Id.

Robert returned to Dr. Barsh on January 23, 2012, following completion of the amoxicillin.

Pet. Ex. 1 at 35. He was still coughing; he also had dry skin behind both knees, moles on his back,

and breakthrough seizures. Id. Dr. Barsh’s impression was seizures, dermatitis, and moles; he

recommended a referral to Dr. Mattison for a mole check and cortisone for the dermatitis. Id. Blood

work revealed high cholesterol, high eGFR, low MPV, and eosinophils at 6.0 on a scale of 0.0 to

6.0, the high end of normal. Id. at 57-59. Robert was also vitamin D deficient. Id. at 57.

Robert returned to Dr. Barsh on January 27, 2012 with persisting cough. He was breathing

comfortably. Pet. Ex. 1 at 36. He was prescribed 500 mg of Zithromax daily for five days and

50,000 units of Drisdol20 once per week for 12 weeks for vitamin D deficiency. Id. A bone

metabolism workup was recommended. Id.

On February 2, 2012, Robert was presented to Dr. Tsay for “severe vitamin D deficiency.”

Pet. Ex. 1 at 37. Dr. Tsay discussed with Robert’s father the risk for “hungry bone syndrome”21

and subsequent hypocalcemia following vitamin D replacement. Id. Dr. Tsay recommended

supplementing with calcium for a few weeks and then rechecking Robert’s vitamin levels. Id.

20

Drisdol is the brand name for ergocalciferol, a sterol naturally occurring in fungi and some fish oils; it is

administered orally or added to food as a source of vitamin D. Drisdol, DORLAND’S at 567; ergocalciferol,

id. at 640.

21

“Hungry bone syndrome” is the rapid deposition of calcium in bones which results in hypocalcemia.

Hungry bone s., DORLAND’S at 1833.

10

On February 9, 2012, Robert was brought to the NWHC emergency room via ambulance

after having a seizure on the school bus. Pet. Ex. 2 at 32, 35. EMS personnel reported that he was

sluggish but awake upon their arrival. Id. at 32. He had a longstanding seizure disorder, severe

autism, and was minimally verbal. Id. A chest x-ray showed right upper lobe perihilar infiltrate,

likely suggestive of pneumonia. Pet. Ex. 1 at 39; Pet. Ex. 2 at 41. The heart was noted to be

“prominent” on the x-ray. Id. Hospitalization was recommended, but Robert’s father stated that

hospitalization with restraints would be “disastrous.” Robert was discharged with a prescription

for Levaquin.22 Pet. Ex. 2 at 33.

The next day, February 10, 2012, Robert was presented to Dr. Barsh for a follow-up. Pet.

Ex. 1 at 40. He was taking 2500 mg of Keppra twice daily. Id. Seizures the day before and that

day were noted. Id. Robert’s dosage of Keppra was increased to five tablets in the morning and six

tablets at night. Id. Dr. Barsh wrote, “We are not going to use a Levaquin (sic) that was prescribed

in the ER right now. We are going to see how Robert does over the weekend.” Id.

On February 22, 2012, Robert was presented Dr. Sweeney for a neurological follow-up for

epilepsy and autism. Pet. Ex. 1 at 41. He was taking 2500 mg of Keppra in the morning and 3000

mg in the afternoon but had another seizure and his parents increased his Keppra, with an extra

pill at night. Id. Robert’s mother expressed concern about the number of moles Robert had and

wanted his vision checked because he had been losing his footing when walking to the bus. Id.

Robert’s father reported that “there has been a slight change in the seizures. [Robert] does stiffen,

and drool and shake, but he used to be tired afterwards. Now, dad states it is as if nothing happened,

he just keeps going on his way.” Id. Because Robert was on such a high dose of Keppra, Dr.

Sweeney did not want to increase the dosage further. Id. at 41-42. She recommended continuing

with one mg of clonazepam at night and 10 mg of Valium in the morning and at night. Id. at 42.

Dr. Sweeney instructed Robert’s parents to bring him back in six months for a follow-up. Id.

On March 30, 2012, a member of Dr. Tsay’s staff entered a note of a telephone call with

Robert’s mother “to remind her [R]obert needs bloodwork done.” Pet. Ex. 1 at 43.

On April 3, 2012, Dr. Barsh’s staff made a note of “OT prescription mailed home.” Pet.

Ex. 1 at 44. The next day, it was also noted, “OT Rx mailed to Laurie Bauer at Bedford Central

School District.” Id. at 45. Another note entered on April 4, 2012, stated “Mr. Yates called for

renewal of medications. As per Dr. Barsh, his Neurologist will be writting (sic) all RX’s now, not

Dr. Barsh. Mrs. Yates notified.” Id. at 46.

On May 15, 2012, Robert was presented to Dr. McBride, a neurologist, for a second opinion

for breakthrough seizures. Pet. Ex. 1 at 47. Dr. McBride noted that Robert was diagnosed with

developmental delay during his first year of life with no history of febrile seizures, CNS infection,

or head injury. Id. Robert’s first seizure was in November of 2009; he had generalized tonic-clonic

seizures lasting four minutes or less. Id. He was taking 2500 mg of Keppra in the morning and

3000 mg of Keppra at night but was still having breakthrough seizures. Id. He also took 10 mg of

Valium at morning and at night, and one mg of clonazepam at night. Id. He had never had an EEG,

22

Levaquin is the brand name for levofloxacin, a broad-spectrum antibiotic used to treat bronchitis,

community-acquired pneumonia, urinary tract infections, acute maxillary sinusitis, and skin and soft tissue

infections. Levaquin, DORLAND’S at 1031; levofloxacin, id. at 1032.

11

CT, or brain MRI. Id. Robert’s brother also had autism and epilepsy. Id. Dr. McBride noted that it

was uncertain whether Robert’s epilepsy was generalized or secondary to pervasive development

disorder but advised that he needed structural imaging and should have a brain MRI. Id. at 48. Dr.

McBride ordered an MRI and an EEG and added 250 mg of Depakote23 to Robert’s regimen of

seizure medications. Id. at 48-50. Dr. McBride instructed Robert’s parents to bring him back for a

follow-up and blood work in one month. Id. at 48. There were no records filed indicating that the

ordered blood work was ever done.

There were some subsequent notes in Dr. McBride’s records regarding Robert’s

medication. A May 18, 2012 note stated that generic Depakote could be used. Pet. Ex. 1 at 51. A

June 29, 2012 note noted that prescriptions for clonazepam and Valium had an incorrect date; Dr.

Barsh called Dr. McBride’s office for permission to rewrite the prescriptions, which was granted.

Id. at 52. A phone message from Robert’s father on July 23, 2012 asked for a return phone call

regarding a renewal of Keppra. Id. at 53. There was no indication of whether this call was returned.

Robert was returned to Dr. Barsh on July 27, 2012 for his 18-year-old examination. Pet.

Ex. 1 at 54. Dr. McBride was following him for pervasive delay and epilepsy. Robert was taking

Valium, Keppra, Depakote, and Klonopin. Id. He was noted to be a healthy 18-year-old with

pervasive delays and epilepsy but doing well on his current medications. Id. Dr. Barsh encouraged

Robert’s father to speak to the school to ensure Robert had an hour of physical activity every day.

Id. Blood work was ordered and a Menactra vaccine was administered after a discussion of the

risks, benefits, and side effects was had with his father. Id. Blood work results showed positive

Lyme titer, vitamin D deficiency, high cholesterol, high eGFR, high ALT, high MCHC,24 low

MPV, and high eosinophils of 9.4 on a scale of 0.0 to 6.0. Id. at 64-65.

B. Robert’s Medical Records after the Menactra Vaccine.

On July 30, 2012 at 3:48 p.m., Pound Ridge Police Officer Thierstein was dispatched to

the Yates’ home for a report of an eighteen-year-old who was not breathing and had a history of

seizures. Pet. Ex. 22 at 1. Upon arrival, Officer Thierstein was taken by Robert’s brother to a

bedroom where Robert’s parents were administering CPR. Id. According to Officer Thierstein,

Robert was unresponsive and did not appear to be breathing but did have a faint pulse. Id. Officer

Thierstein “assembled the BVM25 and connected it to high flow oxygen.” Id. He instructed Mr.

Yates to stop CPR so that he could use the BVM, but Mr. Yates refused. Mrs. Yates “stated that

the only way that they were going to save their son was for [Mr. Yates] to continue giving breaths

while she continued compressions. [Mrs. Yates] stated that this has happened before and that they

have saved their son Robert Yates in the past by doing what they are doing.” Id. The EMTs arrived

and also tried to use the BVM, but Mrs. Yates refused, stating that “her husband could do a better

23

Depakote is the brand name for divalproex sodium, a medication used in the treatment of epileptic

seizures, particularly absence seizures. Depakote, DORLAND’S at 490; divalproex sodium, id. at 558.

24

Mean Corpuscular Hemoglobin Concentration (“MCHC”) is a measure of the average concentration of

hemoglobin within a single red blood cell. Mosby’s at 400. Elevated MCHC levels are usually attributed to

alteration in red blood cell shape, which may confuse automated counting machines. Id. at 401.

25

“BVM” stands for bag valve mask. BVM, NEIL DAVIS, MEDICAL ABBREVIATIONS 100 (16th ed. 2020).

12

job.” Id. Robert was transported to NWHC by ambulance. Id. Officer Thierstein documented that

Mrs. Yates “stated that this was not the first time something like this has happened but it was the

most serious occasion to date.” Id. She advised she had checked on Robert around 2:30 p.m. and

he was sitting at his desk playing on the computer. Id. “[J]ust prior [to] the 911 call she checked

on her son and he was slumped down in the chair at his desk and did not appear to be breathing.”

Id. Officer Thierstein’s report documented that Trooper Yorke and Investigator Merritt responded

to the scene to investigate. Their investigation reports were not filed into the record.

The ambulance record documents receipt of an emergency call at 3:48 pm and arrival at

the Yates’ home at 3:57 pm. Pet. Ex. 4 at 5. Robert was lying on the floor with CPR in progress.

Id. Mrs. Yates reported that she “found patient slumped in front of his computer [and] pulseless

apneic unconscious unresponsive. Unknown down time.” Id. EMS personnel noted that Robert

had pedal edema and his skin was cyanotic with delayed capillary refill. Id. Parents “tried to give

patient lorazepam orally prior to EMS.” Id. The EMTs were unable to intubate him due to a swollen

tongue. Id. at 6. EKG showed asystole.26 Epinephrine and sodium bicarbonate were administered,

and CPR was continued during transport with no change. Id. The ambulance departed the Yates’

home at 4:17 p.m. and arrived at NWHC at 4:31 p.m. Id. at 5. Despite extensive attempts at

resuscitation in the ER, Robert was pronounced dead at 4:57 pm. Pet. Ex. 2 at 6-8. Robert’s death

certificate listed the immediate cause of death as lymphocytic myocarditis (pending further study).

Id. at 4.

C. The Autopsy Report

The autopsy report documented an 18-year-old male with pervasive developmental

disorder and generalized tonic-clonic seizures found unresponsive in his room at home. Pet. Ex. 3

at 13. His mother reported that he had a seizure that day and was given dissolvable clonazepam.

Id. He had received a second dose of meningococcal vaccine on Friday, July 27, 2012. Id. His

seizures were controlled with levetiracetam, diazepam, clonazepam, and Depakote. Id.

An examination of the heart showed mild hypertrophy of the left ventricle and mild dilation

of the right ventricle. Pet. Ex. 3 at 13. Tissue samples were taken from the left ventricle, septum,

and anterior, lateral, and posterior walls. Id. Microscopic examination of those samples showed

evidence of subepicardial myocarditis; there was lymphocytic inflammatory infiltrate with focal

myocyte necrosis.27 Id. The report further noted interstitial fibrosis with scant lymphocytes. Id.

There was no ischemia,28 myocardial fiber hypertrophy, or fibrosis. Id. The other samples were

unremarkable but for focal thinning and focal loss of striation of the myocardial fibers. Id. Tissue

samples of the AV node were unremarkable and free of fibrosis, inflammation, granuloma, or

26

Asystole is cardiac standstill or arrest; the absence of a heartbeat. Asystole, DORLAND’S at 170.

27

The autopsy showed that there was inflammation of the outer muscular heart wall with deposits of white

blood cells responsible for humoral and cellular immunity and sites of muscle cell death. Myocyte,

DORLAND’S at 1222; myocarditis, id. at 1221; necrosis, id. at 1235; lymphocyte, id. at 1084; infiltrate, id.

at 936.

28

Ischemia is a deficiency of blood to a body part, usually due to functional constriction or actual

obstruction of a blood vessel. Ischemia, DORLAND’S at 961.

13

tumor. Id. The lungs were normal; there was vascular congestion with fresh intra-alveolar

hemorrhages. Id. The sections were free of inflammation, emphysema, fibrosis, or malignancy. Id.

The bronchus and bronchioles were unremarkable. Id. There were fatty changes of the liver. Id.

The cause of death was lymphocytic myocarditis, natural. Pet. Ex. 3 at 10.

D. Mrs. Yates’s First Affidavit and Testimony

Mrs. Yates submitted an affidavit prior to hearing and testified at hearing.

Mrs. Yates testified that she has four sons; two with autism. Tr. 11. Mrs. Yates stated

Robert developed epilepsy at age 16, while her other son with autism developed epilepsy at 14;

she believes it had something to do with puberty. Tr. 13. She affirmed that Robert had “some

neurological issues and seizures” but “no serious or life-threatening illnesses.” Pet. Ex. 10 at 1. He

was healthy and under the care of physicians for his seizures. Id.

Mrs. Yates stated that Robert had good receptive language, but communicated as children

with autism do, in different ways. Tr. 15. He would not tell her if he had a sore throat or a headache;

“[i]t was up to me to guess first.” Tr. 15-16. She could not take “their” temperature, referring to

her “youngest children” with autism. Tr. 16.

According to Mrs. Yates on July 27, 2012, Mr. Yates picked up Robert from school after

a half day and took him to the doctor for a routine physical. She was home with their other autistic

son. Tr. 12-13; Pet. Ex. 10 at 1. Robert had blood taken and received his second Menactra

vaccination at this appointment. Tr. 14-15; Pet. Ex. 10 at 1. She did not know the results of the

blood work but believed it was normal, because she did not receive a telephone call stating

otherwise. Tr. 14. Mrs. Yates affirmed, “Dr. Barsh gave a favorable medical report and

recommended that [Robert] exercise for an hour a day at school. No medications were prescribed

for [Robert].” Pet. Ex. 10 at 1. She affirmed that Robert came home with a Band-Aid. Id. She was

not warned about any possible side effects of the vaccination. Id.

Mrs. Yates affirmed that the remainder of that day was normal, Robert spent time on the

computer and watched television. Pet. Ex. 10 at 1. At hearing, she recalled Robert had received a

Leapfrog book, a battery-operated book that reads to you, either that day or Saturday, and spent a

lot of time using it. Tr. 17. She recalled nothing unusual the next day, July 28, 2012. Tr. 18-19.

She then stated she was unsure which day it was, Saturday or Sunday, but Robert slept more than

usual. Tr. 20. However, she sent him to school on Monday, which was a half day. She would not

have sent him to school if he was not alright. Tr. 20-21.

According to Mrs. Yates on July 30, 2012, Robert came home from school around 12:30

p.m. and went to his room to play on the computer. Pet. Ex. 10 at 1-2. She looked in on him

between 12:30 and 3:30 p.m., he was still on the computer. Id. at 2. When Mr. Yates came home

around 3:30 p.m., she went to check on Robert and found him passed out with his headphones on

seated at his computer with his head on the keyboard. The computer screen was black with the

exception of a white square. Id. She screamed for Mr. Yates who came and started “mouth-to-

mouth” while she did CPR. Id. Ian, her other son, made the emergency call. Id. The police arrived

14

with a balloon lung inflator, “but it was of no help.” Id. Mr. and Mrs. Yates continued “our

ministrations for about 45 minutes until the ambulance arrived” and took they Robert to NWHC.

Id. Mr. Yates went in the ambulance with Robert, she stayed home with her other sons, Ian and

Dylan. Tr. 22.

Mrs. Yates agreed that Robert’s cause of death was lymphocytic myocarditis. Pet. Ex. 10

at 2.

Mrs. Yates stated that she filed a VAERS report but never heard from anyone. Tr. 26; Pet.

Ex. 20. The VAERS report filed was consistent with Mrs. Yates’ testimony; however, there was a

letter attached to her filing showing a response addressed to her from VAERS. Pet. Ex. 20 at 3-4.

E. Mrs. Yates’s Post-Hearing Affidavit

Petitioner submitted a second Affidavit following the hearing to address the contents of the

police report.29

According to Mrs. Yates, Robert was never given CPR prior to July 30, 2012, nor was he

ever taken to the hospital for a similar episode. ECF No. 63 at 1. “Robert was epileptic and on

several occasions when he had an epileptic fit we would administer” clonazepam “and his epileptic

fits would stop.” Id.

Mrs. Yates recounted an occasion in 2006 when her son Dylan, who also has epilepsy, was

admitted to NWHC and while there had another “fit” and Mr. Yates did CPR. ECF No. 63 at 1.

The nurses encouraged Mr. Yates to continue doing the CPR, saying “Keep going! You are doing

great!” Id. at 1-2. Dylan recovered from this episode. Id. at 2. Mrs. Yates affirmed, “I believe this

is what the Pound Ridge police report is referring to when it states that I had made mention of Mr.

Yates being able to save his son before by performing CPR.” Id.

Mrs. Yates added that the BVM comes in two pieces and neither the police officer nor the

EMTs appeared to know how to put it together. ECF No. 63 at 2. She and Mr. Yates had been

doing CPR for several years by then. Id. They were not required to learn CPR or taught to perform

CPR for any specific reason. Id.

IV. The Experts’ Opinions

A. Petitioner’s Experts

1. Dr. Anthony Chang

i. Qualifications

Dr. Anthony Chang is the director of the Heart Institute at Children’s Hospital of Orange

County. Pet. Ex. 9 at 3. He holds an undergraduate degree in molecular biology from Johns

Hopkins University and a medical degree from Georgetown University Medical School. Id. at 1.

29

Mrs. Yates’ second affidavit was not filed as an exhibit and is cited herein as “ECF No. 63.”

15

He did a fellowship in pediatric cardiology at the Children’s Hospital of Philadelphia and worked

as a cardiologist at Boston Children’s hospital. Tr. 186; Pet. Ex. 9 at 1. He is board certified in

pediatrics and pediatric cardiology. Pet. Ex. 9 at 2. Dr. Chang has been a cardiologist for over 30

years; he estimated that he consults on or sees 10 to 25 children with myocarditis per month, over

a thousand cases per year. Tr. 186-87. He estimated that over the span of his career, he has dealt

with anywhere from 3,000 to 10,000 cases of myocarditis or myocardial inflammation. Tr. 187.

His areas of interest have included cardiac intensive care and heart failure in children; both areas

deal with myocarditis of all types. Tr. 186. In addition to his clinical experience, Dr. Chang has

written several manuscripts on myocarditis and coedited a supplement on myocarditis on behalf

of the Pediatric Cardiac Intensive Care Society, which he founded. Tr. 186. Dr. Chang was also

the chief editor of a 2006 textbook, Heart Failure in Children and Young Adults: From Molecular

Mechanisms to Clinical and Surgical Strategies, in which he edited the chapter on myocarditis.30

Tr. 186; Pet. Ex. 9 at 34.

In addition to his medical degree, Dr. Chang holds an MBA from University of Miami

School of Business, an MPH from University of California at Los Angeles School of Public Health,

and an MS in Biomedical Informatic/Artificial Intelligence from Stanford School of Medicine. Id.

ii. Causation Opinion

Dr. Chang opined that Robert suffered from myocarditis secondary to the Menactra

vaccine. Pet. Ex. 6 at 2.

Dr. Chang explained that myocarditis is an inflammation of the heart muscle caused by

different types of cells involved in fighting off infection or responding to a foreign substance. Tr.

188. The heart responds to inflammation by swelling; it becomes enlarged and less able to contract

and relax normally. Tr. 188-89. If the inflammation affects the heart’s conduction system, it can

trigger a sudden cardiac event. Tr. 188-89. Inflammation of the heart can be acute, from within

minutes to hours, to chronic, over months and years. The faster the onset of inflammation, the

worse the patient’s prognosis, because the changes in the heart’s performance occur too quickly

for the body to adapt. Tr. 189.

In Dr. Chang’s opinion, Robert had an inflammatory response to the Menactra vaccine

which led to a hypersensitivity or generalized inflammatory process that affected his heart and

caused sudden cardiac arrhythmia and sudden cardiac death. Tr. 189.

Dr. Chang explained that Menactra vaccine induces an immune response using a weakened

version of the bacteria, “so that when the real disease hits, the immune response is ready to attack

the offending agent.” Tr. 200. He stated anytime a foreign substance, medication, drug, or object

is introduced into the body, you have an inflammatory response; usually the response is small, but

sometimes it can be severe. Tr. 201-02. Dr. Chang has never seen an instance of a child dying of

heart failure from a vaccine but has heard that cases of myocarditis have been reported secondary

to the smallpox vaccine. Tr. 201.

Dr. Chang opined that, because Robert had previously received a Menactra vaccine in

30

Petitioner did not file any excerpts from the chapter on myocarditis or this textbook into the record.

16

2005, his body had a biological memory for the vaccine, which caused him to have a more severe

and accelerated reaction to the vaccine. This type of reaction could be referred to as a Type IV

hypersensitivity response. Tr. 194-95. According to Dr. Chang, the elevated eosinophil count in

Robert’s bloodwork performed on the date that he received the second Menactra vaccine shows

that the inflammation, or response to the vaccine, was already beginning. Tr. 192-93; see also Pet.

Ex. 11 at 4 (“Of note, there was an elevated eosinophil count on the peripheral white blood cell

profile (9.4%) to indicate that there is most likely a hypersensitivity inflammatory process that is

generalized”).

When asked how Robert could have had a hypersensitivity reaction when he had no

symptoms of vomiting, swelling, difficulty breathing, or any other sign of an ongoing reaction, Dr.

Chang responded, “

Well, the heart sometimes…is the most vulnerable organ because it doesn’t have

sometimes a very active process to mediate the immune response. So,

unfortunately, if the conduction system of the heart, the electrical wiring of the

heart, is affected, unfortunately that could be lethal, even if it’s not a severe

inflammation that you’ll see in the rest of the body.”

Tr. 225.

Dr. Chang opined that Robert suffered from acute fulminant31 myocarditis because “[t]he

patient died in two to three days after administration of a substance.” Tr. 210. He stated, “This is

acute fulminant myocarditis, by definition, because the patient died within days of an onset of

inflammation, and time course-wise, the only thing would make biomedical sense would be the

vaccine.” Tr. 217. A patient can have a hypersensitivity response, but still “have the same clinical

diagnosis of essentially a very acute…fulminant clinically, acute fulminant myocarditis.” Tr. 197.

He characterized Robert’s myocarditis as “acute fulminant myocarditis, plus/minus

hypersensitivity, because of the rapid acceleration of the disease process….” Tr. 197.

In support of his theory, Dr. Chang submitted one case report in which a 17-year-old boy

was admitted to pediatric intensive care with complaints of myalgias, chest pain, and low-grade

fever two days after receipt of DTaP, meningococcal conjugate, and hepatitis A vaccinations and

subsequently diagnosed with myocarditis. Pet. Ex. 8 at 1-2.32 The authors noted that the possibility

of a viral etiology could not be excluded even though there was a negative viral serology, but the

absence of symptoms made it less likely. Id. at 2. It was further noted that, in cases of myocarditis

reported after vaccination, a hypersensitivity reaction is usually suspected based on the temporal

link between receipt of the vaccine or other offending agent and the onset of symptoms. Id.

“Pathogenesis is related to a maladaptive immune response that leads to myocardial injury, as

evidenced by biopsy specimens in cases of myocarditis after smallpox vaccination that have

revealed CD3+ T-cell infiltrate with prominent degranulating eosinophils.” Id. at 2-3.

31

“Fulminant” means sudden or severe; occurring suddenly and with great intensity. DORLAND’S at 748.

32

Maria T. Thanjan et al., Acute Myopericarditis After Multiple Vaccinations in an Adolescent: Case Report

and Review of the Literature, 119 PEDIATRICS e1400-03 (2007), filed as “Pet. Ex. 8,” “Resp. Ex. A, Tab

11,” and “Resp. Ex. C, Tab 4.”

17

When asked if timing was the primary reason for his opinion that the vaccine was the cause

of Robert’s myocarditis and death, Dr. Chang initially denied that timing was the only reason but

then stated, “but it would be one of the major supportive evidence for this being a reaction to the

vaccine, that’s correct.” Tr. 211. Throughout the hearing, Dr. Chang repeatedly emphasized the

significance of the temporal relationship between Robert’s receipt of the Menactra vaccine and his

sudden death. See, e.g., Tr. 190 (“The clinical diagnosis in this case in terms of the time course is

very, very relevant to the administration of the vaccine”), 195 (“…the response was very, very

severe in a very short amount of time after a prior exposure to the vaccine”), 203 (“So the fact that

[Robert] took two or three days is very, very consistent with…[an] acute reaction to the vaccine

that is – that was so severe that it affected the heart to the degree that it did”), 205 (“…the timeline

is extremely difficult to challenge that he responded to that severity to the vaccine”).

Dr. Chang refused to differentiate between lymphocytic myocarditis and eosinophilic or

hypersensitivity myocarditis and referred to what Robert suffered from as simply “myocarditis,”

stating myocarditis is a clinical diagnosis rather than a pathological diagnosis. Tr. 190, 191, 217.

He maintained that, as a clinician, more emphasis is placed on treating the patient than labelling

the type of myocarditis the patient suffers from. See, e.g., Tr. 191 (“…it’s not necessary to label

myocarditis as a certain type of myocarditis…”), 192 (“If you want to call it hypersensitivity, you

can. If you want to call it just an acute-onset myocarditis, you can also. No one would be right or

wrong by labeling this differently…”), 197 (“…as a clinical cardiologist, we don’t particularly

care what label any doctor wants to put on the disease process. We have to treat the patient”), 199-

200 (“You want to call it hypersensitivity, acute or acute fulminant myocarditis, to me [it] is just

different experts debating about the label”), 216 (“I don’t care what label you put on it,

hypersensitivity versus – I can easily call this acute fulminant myocarditis”), 218 ( “If you want to

put a label of hypersensitivity on it, it doesn’t – it doesn’t make me want to treat the patient any

different”).

When asked about the distinction made in all of the medical literature that lymphocytic

myocarditis is viral and eosinophilic myocarditis is hypersensitivity or indicative of allergic

response, Dr. Chang stated, “I’m disagreeing with the gross oversimplification that you can

necessarily and correctly put different patients into different categories that conveniently because

not – I guarantee you that not 100 percent of patients are going to follow every single description

for hypersensitivity myocarditis and not 100 percent of patients with lymphocytic myocarditis will

follow all of that either.” Tr. 204-05. He added, “If a patient responds to the vaccine in an

accelerated and severe fashion that leads to essentially a sudden cardiac death, the type of cell is

not going to tell you whether or not it is true or not that the patient responded to the vaccine because

you can have a hypersensitivity kind of reaction without eosinophils.” Tr. 208.

Dr. Chang disagreed with respondent’s experts’ opinions that a diagnosis of

hypersensitivity myocarditis requires the presence of eosinophils in the heart tissue. He opined that

the absence of eosinophils in the heart on autopsy does not preclude acute inflammatory

myocarditis from vaccination. Pet. Ex. 11 at 4; Tr. 208. He added that hypersensitivity myocarditis

is sometimes characterized by the presence of eosinophils, but it is not the only way that a

hypersensitivity myocarditis can demonstrate itself. Tr. 190-91. A vaccination can trigger

inflammation leading to either eosinophilic and/or lymphocytic myocarditis; both are

inflammatory processes. Pet. Ex. 11 at 4. Although you can see eosinophils in a hypersensitivity

18

response, “not 100 percent of patients will have eosinophils in a hypersensitivity response to a

vaccine…we don’t have enough experience with vaccines and hypersensitivity situations [to

know] what percent of the patients will actually have eosinophils.” Tr. 194, 224.

Dr. Chang agreed that Robert’s autopsy showed histopathological evidence of lymphocytic

myocarditis, but in his opinion, a vaccine reaction can cause lymphocytes or eosinophils. Tr. 206,

208. He added, “…this is selected slices of the heart that did not show eosinophils. You can’t just

sort of make a blanket statement and say, well, because a number of slides did not show

eosinophils, there were no eosinophils at all.” Tr. 206. He added that, eosinophils or none, “this is

acute fulminant myocarditis, by definition, because the patient died within days of an onset of

inflammation, and time course-wise, the only thing that would make biomedical sense would be

the vaccine.” Tr. 216-17.

When asked for the literature which supported his statements that hypersensitivity

myocarditis can be characterized histopathologically by lymphocytes, Dr. Chang referenced a

1992 abstract which was filed after the hearing. The abstract was a summary of a 1991 study which

examined autopsy tissue specimens from 69 cases of hypersensitivity myocarditis to determine the

association between the degree of cellular infiltration and cardiac symptoms. Pet. Ex. 24 at 1.33

The authors defined hypersensitivity myocarditis “by the presence of eosinophils, a mixed

lymphohistiocytic infiltrate along natural planes of separation, and an absence of fibrosis or

granulation tissue in areas of infiltrate.” Id. Examination of the cell types showed predominantly

histiocytes, but lymphocytes were present in 12 cases and eosinophils in 30 cases. Id. The authors

concluded that cardiac symptoms were not related to the degree of cellular infiltrate. Id.

Dr. Chang testified that, in determining that the Menactra vaccine caused Robert’s

myocarditis, he considered possible alternate causes. Robert did not have a congenital heart defect

on autopsy. Tr. 212. He considered the effects of Depakote, agreeing that some anticonvulsant

medications can cause hypersensitivity myocarditis. Tr. 199. He stated that it was “absolutely

possible that there was some generalized inflammation that resulted” from the addition of

Depakote to Robert’s medication regimen in May of 2012 but added it was “two or three months

before [Robert’s] demise.” Tr. 199. Therefore, he concluded that the Depakote was unlikely to be

the “offending agent that led to [Robert’s] inflammation and myocarditis” when compared to the

“most obvious reason which is the administration of the vaccine.” Tr. 199, 211-12.

Furthermore, Dr. Chang disagreed with respondent’s position that Robert’s myocarditis

was caused by a viral infection.

While Dr. Chang agreed with Dr. Folkerth that lymphocytic myocarditis is most commonly

caused by infection, he stated a finding of lymphocytes on autopsy does not dictate viral

myocarditis as a cause of death. Tr. 208, 216. He referred to a study of autopsies of military

personnel who did not die of myocarditis but still had lymphocytes in the heart on autopsy. 34 Tr.

215. In Dr. Chang’s opinion, evidence of a low-grade viral infection on autopsy is “not a rare

33

A.P. Burke et al., Hypersensitivity Myocarditis, 115 ARCH. PATHOL. LAB. MED. 764-69 (1991), filed as

“Pet. Ex. 24.”

34

This study was not filed into the record for consideration.

19

finding…So it would be grossly erroneous for you to say, well, there are lymphocytes here so this

patient died from viral myocarditis. That, I would be shocked if astute clinicians would say that.”

Tr. 215-16.

Rather, Dr. Chang stated the etiology of a patient’s myocarditis should be based on the

clinical history and other types of evidence, such as a viral panel and white blood cell count. Pet.

Ex. 11 at 4. “I’ve never, ever seen a patient that dies from acute fulminant myocarditis from a

virus, and yet was totally asymptomatic and had no infectious agent detected on any testing. That

would be – that would be extremely rare.” Tr. 198, 213. Dr. Chang added it is “theoretically

possible” that Robert had a subclinical myocarditis that coincidentally developed at the same time

the vaccine was received but it is “simply highly unlikely” because Robert’s laboratory data and

peripheral white blood cell count was “entirely normal without any supportive evidence of a viral

infection.” Pet. Ex. 11 at 4 (emphasis in original). Dr. Chang concluded that a diagnosis of

hypersensitivity myocarditis “is now (sic) substantiated by the presence of these lymphocytes at

the -- on the slides, in the specimen, but the time course, the presentation, the lack of any sign or

symptom of viral infection makes it much more likely that this is a reaction.” Tr. 191-92. “By far

and away the most likely etiologic agent is the vaccine, not anything else.” Tr. 213. Dr. Chang

repeatedly stated that there was no sign of viral infection but did not address the fact that the

Luminex Virus Panel Assay was never performed. Tr. 191, 197-98, 208, 211.

2. Dr. Laurel Waters

i. Qualifications

Dr. Laurel Waters received a Bachelor of Science from the University of California at

Berkeley and a medical degree from the University of California at Davis. Pet. Ex. 19 at 1. She is

board certified in pediatric pathology, nuclear medicine, and anatomic and clinical pathology.35

Id. She is an assistant clinical professor at the University of California Davis School of Medicine

in the Department of Pathology and Laboratory Medicine. Pet. Ex. 19 at 1. Dr. Waters described

her duties at UC-Davis as “didactic and other types of teaching” rather than teaching students how

to perform autopsies. Tr. 31. Although she has done “numerous” autopsies in her career, she has

not performed an autopsy in “[a] couple of years,” and was unsure of the last time she did an

autopsy. Tr. 31, 33. In the past, she has probably reviewed “a dozen or so” slides on myocarditis.

Tr. 34. Dr. Waters is not affiliated with, nor does she have privileges at, any hospital Tr. 32.

Dr. Waters also has a business in which she does expert witness work and medical/legal

consultation; some of her work is for government agencies, and sometimes she consults with

families to help them understand the process of disease and determine “whether they have a case

or not.” Tr. 31, 63. Consulting is about half of her income. Tr. 64. Dr. Waters does presentations

but hasn’t “been into publishing.” Tr. 62.

Dr. Waters stated that in addition to her specialty in pediatric pathology, she has some

background in immunology, having done some research in immunology through the early parts of

35

A pathologist is a physician who interprets and diagnoses the changes caused by disease in tissues and

body fluids. Pathologist, MERRIAM-WEBSTER ONLINE DICTIONARY, https://www.merriam-

webster.com/dictionary/pathologist (last visited Mar. 23, 2020).

20

her career. Tr. 144. She has “kept up on immunology.” Tr. 144. She stated, “I have an

immunologist’s kind of perspective as well as a pathologist kind of perspective.” Tr. 144. She was

asked to clarify her background in immunology, since her CV did not contain anything

immunology related. Tr. 148. Dr. Waters stated that she did “a lot of research that involved cell-

mediated cytotoxicity, looked at cytokines, lymphokines specifically; used a murine model

where—asplenic murine model where I was doing in vitro tissue culture with mouse spleens.” Tr.

148. She explained that this research was conducted during her training at UC-Davis in 1978 and

UC-Berkeley in 1974. Tr. 148-49.

ii. Causation Opinion

Dr. Waters opined that Robert had an anamnestic T-lymphocyte cell response to the

Menactra vaccine, which caused his myocarditis and subsequent death. Pet. Ex. 13 at 7. She

explained that “[a]namnestic responses to a subsequent exposure to an antigen are quicker and

more intense” noting Robert’s prior Menactra vaccination in 2005. Id. at 3, 7. The Menactra

vaccine is T-lymphocyte mediated, which, in Dr. Waters’ opinion, correlates with the lymphocytic

cells found in Robert’s heart. Id. at 6-7. She further opined that his death three days after

vaccination is consistent with other vaccine-caused myocarditis cases. Id. at 8.

Dr. Waters proposed that Menactra is a quadrivalent meningococcal polysaccharide protein

conjugate; it is T-lymphocyte dependent, which means that the immune system responds to the

vaccine by generating T-lymphocytes. Pet Ex. 13 at 5-6; Tr. 56. When asked to explain what this

means, Dr. Waters testified, “

…the body responds to Menactra by producing T-lymphocytes which have memory

associated with—with the mixture of the protein and the polysaccharide that this

vaccine had. The initial vaccines did not have the protein conjugate. And, so this

was found to be much superior, but what—what happens is that there—that’s just

an explanation of what the mechanism of the body’s response is to the vaccine and

how it is mediated.”

Tr. 87-88. After the hearing, Dr. Waters submitted a study containing the quote, “Meningococcal

conjugate vaccines, through conjugation of polysaccharide to a protein carrier, changes the

immune response from T-cell independent to T-cell dependent, leading to improved

immunogenicity over polysaccharide vaccines.” Pet. Ex. 21 at 1.36 The study examined VAERS

reports of pregnant women who received Menactra vaccinations; it did not identify any safety

concerns. Id. at 1, 5.

Dr. Waters stated that myocardial inflammation can affect the atrioventricular node, which

regulates heart rhythm via electrical stimulant; “involvement of the node can cause a dysrhythmia

and sudden death.” Tr. 38-39. Myocardial inflammation “may be due to lymphocytes and

macrophages and [is] histologically termed lymphocytic myocarditis.” Pet. Ex. 13 at 6. In her

36

Yenlik Zheteyeva et al., Safety of Meningococcal Polysaccharide-Protein Conjugate Vaccine in

Pregnancy: a Review of the Vaccine Adverse Event Reporting System, 208 AM. J. OBSTET. GYNECOL.

478.e1-6 (2013), filed as “Pet. Ex. 21.”

21

report, Dr. Waters wrote, “[l]ymphocytes gravitated to the heart’s conduction system causing a

lethal arrhythmia and sudden death.” Id. at 7. At hearing, she testified that, because Menactra

works through a response of T-lymphocytes, “[t]he fact that we have a lymphocytic response is

certainly very consistent with the cause being the vaccine and the time course is appropriate.” Tr.

56-57. When asked if she had any evidence that the lymphocytes created in response to Menactra

would gravitate to the heart’s conduction system, Dr. Waters cited to a textbook excerpt which

states “Myocarditis may be found in a significant number of cases of meningococcal sepsis,

sometimes with involvement of the atrioventricular node.” Pet. Ex. 18 at 8;37 Tr. 73. However, this

textbook discussed myocarditis from actual meningococcal bacterial disease and sepsis; it did not

discuss the meningococcal vaccine. When asked whether she had any evidence specific to the

Menactra vaccine, Dr. Waters responded, “I don’t have that. As I said, I found it in the – in – since

I found it in the package insert, I thought that was in the record.” Tr. 73. The Menactra package

insert, filed as Pet. Ex. 26, does not discuss whether lymphocytes created in response to Menactra

would gravitate to the heart’s conduction system. When asked if there was any literature supporting

meningococcal vaccine causing lymphocytic myocarditis, Dr. Waters again referenced the

Menactra package insert, stating the mechanism of action for the vaccine is through T-

lymphocytes. Tr. 78. The package insert does not discuss myocarditis.

In her report, Dr. Waters noted that Robert’s autopsy showed “a significant sized focus of

inflammation in the heart which was primarily mononuclear with lymphocytes and macrophages…

This is lymphocytic myocarditis, which is the most common histologic type of myocarditis.” Pet.

Ex. 13 at 4. Dr. Waters appeared to disagree with Dr. Chang’s opinion that Robert suffered from

an acute hypersensitivity myocarditis, noting “[t]his clinical pattern of myocarditis is shown under

the microscope to have eosinophils” while “[t]he predominant cell type in Robert’s heart was

lymphocytes under the microscope, so it is histologically diagnosed as lymphocytic myocarditis.”

Id. at 7. When questioned, Dr. Waters agreed that histologically, there were only lymphocytes in

Robert’s heart on autopsy, with no evidence of eosinophils, but in an apparent attempt to agree

with Dr. Chang, she added that a “clinical diagnosis of hypersensitivity myocarditis is not always

accompanied by eosinophilic myocarditis under the microscope. It may have a predominance of

lymphocytes, so that is not a way to separate out hypersensitivity.” Tr. 35-36, 69.

Dr. Waters also discussed eosinophilic myocarditis in her report. She explained that

“eosinophilic or hypersensitivity myocarditis…shows a mixed inflammatory cell infiltrate which

includes eosinophils” and is sometimes associated with eosinophils in the peripheral blood. Pet.

Ex. 13 at 6. She posited this is an allergic-type reaction; a person with this type of myocarditis may

exhibit other clinical signs of allergic response. Id. She further stated that, clinically, when there

is no peripheral eosinophilia, differentiating between lymphocytic and eosinophilic myocarditis

depends on examination of the heart tissue by endomyocardial biopsy or autopsy. Id. At hearing,

Dr. Waters agreed that it is possible to differentiate between lymphocytic myocarditis and

eosinophilic myocarditis when examining tissue slides under a microscope. Tr. 35. She further

conceded that evidence of eosinophils in heart tissue would indicate eosinophilic myocarditis,

while the absence of eosinophils would preclude a finding of eosinophilic myocarditis. Tr. 149-

50.

37

ROGER W. BYARD, SUDDEN DEATH IN THE YOUNG 181-83, 197-99, 212, 215-16, 220, 256-57 (3rd ed.

2010), filed as “Pet. Ex. 18.”

22

In support of her opinion that the Menactra vaccine caused Robert to suffer from

lymphocytic myocarditis, Dr. Waters submitted the Ball38 and Barton studies. Tr. 73-74, 75; Pet.

Ex. 13 at 5-6; Pet. Ex. 16; Pet. Ex. 17.

Ball studied the safety of the meningococcal vaccine by examining reports of serious

adverse events made through VAERS between 1990 and 1999. Pet. Ex. 16 at 2.39 During that time,

over six million doses of meningococcal vaccine were distributed in the U.S. and 264 adverse

events were reported, 38 of which were considered serious. Id. at 2-3. Ball concluded that these

statistics were “reassuring with regard to the safety of the meningococcal vaccine.” Id. at 8. Of 11

reports of serious adverse events from outside the U.S., there was one report of myocarditis the

day after immunization in an eight-year-old boy. Id. at 6. At hearing, Dr. Waters agreed that it was

not determined whether that boy suffered from hypersensitivity or lymphocytic myocarditis. Tr.

74.

Barton was a case report on two children who developed eosinophilic myocarditis, one

after meningococcal vaccination and one after hepatitis B vaccination. Pet. Ex. 17 at 1-2.40 Both

children manifested noncardiac symptoms the day of or the day after immunization and cardiac

symptoms three to ten days after immunization. Id. at 4. Barton noted that eosinophilic myocarditis

infrequently arises from allergic or autoimmune triggers and “has a distinctive pattern of

eosinophilic inflammatory infiltrates that characterize the entity.” Id. at 1. In both cases, a

myocardial biopsy indicated eosinophilic myocarditis. Id. at 2-3.

Barton specifically stated that hypersensitivity myocarditis, which can occur after

administration of various pharmaceutical agents, including vaccines, is characterized by a finding

of eosinophilic infiltrate, “as opposed to a lymphocytic infiltrate, characteristic of viral etiology.”

Pet. Ex. 17 at 4. Barton further noted that other reports of cardiac injury associated with common

vaccines supported an immune-mediated hypersensitivity mechanism. Id. However, Barton noted,

“clinical, laboratory, and myocardial biopsy findings are indistinguishable between postvaccine

and drug-induced myocarditis.” Id. Patient Two received penicillin four weeks before vaccination

and therefore a drug-induced myocarditis could not be excluded. Id.

Barton noted that one potential mechanism was a Type III hypersensitivity immune

complex-mediated reaction, which usually occurs within one to two weeks of exposure. Pet. Ex.

17 at 4. Barton suggested that this mechanism was applicable to bacterial vaccines such as

meningococcal vaccine, based on Patient Two’s biopsy results showing immune complexes of

meningococcal polysaccharide, IgG antibodies, and complement deposits in myocardial tissue and

low serum complement. Id. Barton determined that the “characteristic eosinophilic infiltrate”

present in both patients in this case report supported an allergic etiology. Id.

38

The Ball study was incorrectly referred to as “Bell” in both Dr. Waters’ report and at hearing. See Pet.

Ex. 13 at 5; Tr. 74.

39

Robert Ball et al., Safety Data on Meningococcal Polysaccharide Vaccine from the Vaccine Adverse

Event Reporting System, 32 CLIN. INFECT. DIS. 1273-80 (2001), filed as “Pet. Ex. 16.”

40

Michelle Barton et al., Eosinophilic Myocarditis Temporally Associated With Conjugate Meningococcal

C and Hepatitis B Vaccines in Children, 27 PEDIATR. INFECT. DIS. J. 831-35 (2008), filed as “Pet. Ex. 17.”

23

Dr. Waters agreed that both patients discussed in Barton had myocardial biopsies showing

eosinophilic infiltrate rather than lymphocytic infiltrate. Tr. 77-78. When asked to confirm that

Barton found, to the extent that evidence existed for an association between myocarditis and the

meningococcal vaccine, it would be eosinophilic, not lymphocytic myocarditis, Dr. Waters

hedged, “[Barton] suggests that in two out of their two cases the eosinophilic part was

histologically seen.” Tr. 77-78. While Dr. Waters agreed that the eosinophilic infiltrate Barton

found was caused by a hypersensitivity phenomenon, as opposed to lymphocytic infiltrate, which

is characteristic of a viral etiology, she stated this only applies to a Type I hypersensitivity reaction,

not the Type IV reaction she is opining occurred in Robert. Tr. 78-79.

Dr. Waters further agreed that the articles she relied on referred to eosinophilic myocarditis,

not lymphocytic, when discussing vaccine-related myocarditis, but she stated basic textbooks state

that vaccines can cause lymphocytic myocarditis. Tr. 80-81. When asked where those textbook

references were in the record, she stated that she did not submit them because “it just seemed to

be something that was so generally included in knowledge--” Tr. 81.41

Although not included in her written report, Dr. Waters opined at hearing that Robert

suffered from a hypersensitivity reaction to the Menactra vaccine in agreement with Dr. Chang.

Tr. 55-56. She based this opinion on the presence of lymphocytes in the myocardium, the lack of

evidence of viral infection, and his death three days after vaccination. Tr. 55-56.

In Dr. Waters’ opinion, the difference between a hypersensitivity response and

lymphocytic myocarditis is that one term is histologic and the other is clinical. Tr. 76.

Hypersensitivity myocarditis is a “clinical diagnosis” and can occur as an allergic or

hypersensitivity response known as Type I, which involves eosinophils and the immunoglobulin

IgE, or as a Type IV, which involves lymphocytes that react to viruses, “various toxins and so

forth. And that’s delayed type hypersensitivity.” Tr. 35, 152.

More specifically, she stated Type I hypersensitivity reaction is evidenced by eosinophils

and can occur within hours or it can extend out for days. Tr. 48, 51, 79. The reaction could have

symptoms, but if it is not a “strong Type I reaction,” the patient may not display eosinophils. Tr.

86. Dr. Waters offered the blood work performed the day of Robert’s vaccination, stating it was

“taken a few hours after” Robert received the second Menactra vaccine and showed elevated

eosinophils consistent with a very rapid Type I response. Tr. 36, 54. She postured that, if an IgE

level had been measured, it would have increased as well. Tr. 36. She stated Robert’s eosinophil

level on that day was 9.4%, a significant increase of 50% from his blood work six months earlier,

which showed an eosinophil level of 6.0%, “at the upper limit of normal.” Tr. 51-52. Dr. Waters

relied on a 2017 study which defined the characteristics, treatment, and outcomes of eosinophilic

myocarditis in the context of hypersensitivity reactions noting histologically, peripheral

eosinophilia was absent in about 25% of patients with eosinophilic myocarditis. Pet. Ex. 25 at 1,

9.42 “In particular, the high-risk group of patients with hypersensitivity eosinophilic myocarditis

41

Petitioner was ordered to produce the textbooks that Dr. Waters referred to which state that vaccines can

cause lymphocytic myocarditis. All of the literature filed post-hearing referred to eosinophilic myocarditis.

42

Michaela Brambatti et al., Eosinophilic Myocarditis Characteristics, Treatment, and Outcomes, 70 J.

AM. COLL. CARDIOL. 2363-75 (2017), filed as “Pet. Ex. 25.”

24

with the highest occurrence of cardiac arrest and in hospital death can frequently lack peripheral

eosinophilia (up to 35 to 40% of cases).” Id. at 9-10.

Dr. Waters was asked how the eosinophils in Robert’s blood work could elevate so quickly

from 6.0% to 9.4% when the blood work and vaccine were given at the same doctor’s visit and

around the same time. Tr. 59-60. She stated death from anaphylaxis due to eosinophils within

minutes of exposure to an antigen by someone who is hyperallergic would cause the eosinophils

to increase quickly. Tr. 60. She added that, while it was possible that Robert’s medication was

responsible for the rise in eosinophils, an acute increase to 9.4% on the same day as the vaccine

would not have been from his medication. Tr. 60-61.

When asked how eosinophils played any role in Robert’s myocarditis, Dr. Waters stated,

“I didn’t say they did…clinically because we had eosinophils there was an immediate

hypersensitivity reaction. I didn’t see any evidence in the heart, so it either subsided or it was seen

elsewhere that I couldn’t see.” Tr. 70. “But it clearly does not rule out that there was an eosinophilic

reaction earlier that we just don’t see in the slides. That’s very common that you will have a

trenchant eosinophilic reaction and you might not see the eosinophils in the myocarditis -- in the

heart slides that show myocarditis.” Tr. 53.

When asked how Robert had elevated eosinophils in his blood testing but not on the

autopsy slides, Dr. Waters responded that the autopsy slides were not done on day one “and it also

takes some time for the eosinophils to infiltrate.” Tr. 54. When asked how long it would take for

eosinophils to infiltrate the heart, she stated, “That’s a hard thing to study because it means you’ve

got -- and, so, I don’t think it’s very clearly studied, because you would have to have times between

an exposure to an antigen and then look at a biopsy. And doing endomyocardial biopsies is not a

nontoxic thing to do. There’s risks involved in it…You can’t just do the biopsy, and obviously you

would have to have a very complex study to do an autopsy study.” Tr. 84-85.

Dr. Waters opined that a Type IV delayed hypersensitivity response, or “lymphocytic

hypersensitivity response,” is predominantly characterized by lymphocytes; it “never” has

eosinophils. Tr. 36, 79. This type of reaction can take three days “when it’s what we call an

anamnestic response, where the antigen has been seen prior, so there are memory lymphocytes

present so that they respond within a couple of days of the exposure.” Tr. 48. In Dr. Waters’

opinion, the fact that lymphocytes were seen on Robert’s autopsy is “consistent with an anamnestic

response for a type IV delayed-type hypersensitivity response because there are already memory

cells there.” Tr. 150. She added that Type IV reactions have a wide range of symptoms. Tr. 87.

When asked what literature she relied on in forming her opinion that hypersensitivity

myocarditis can be characterized by only lymphocytes, Dr. Waters stated, “Cardiovascular

pathology texts.” Tr. 66. When further pressed, she stated, “I think it’s at least inferred in the Byard

– I think it may be in the Byard selection that I just submitted.” Tr. 57. She was unable to find that

excerpt at hearing. After the hearing, petitioner submitted Pet. Ex. 23, an excerpt from a pathology

textbook.43 The excerpt contains a “Figure 6-19” displaying two illustrations, (A) “Delayed-type

43

ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE 206 (Vinay Kumar et al. eds., 8th ed. 2010), filed

as “Pet. Ex. 23.”

25

hypersensitivity and immune inflammation” and (B) “T cell-mediated cytolysis.” Pet. Ex. 23 at 3.

The caption reads:

Mechanisms of T cell-mediated (type IV) hypersensitivity reactions. A. In delayed-

type hypersensitivity reactions, CD4+ TH1 cells (and sometimes CD8+ T cells, not

shown) respond to tissue antigens by secreting cytokines that stimulate

inflammation and activate phagocytes, leading to tissue injury. CD4+ TH17 cells

contribute to inflammation by recruiting neutrophils (and, to a lesser extent,

monocytes). B. In some diseases, CD8+ cytotoxic T lymphocytes (CTLs) directly

kill tissue cells.

Id. A paragraph below the caption reads “T Cell-Mediated (Type IV) Hypersensitivity – The cell

mediated type of hypersensitivity is initiated by antigen-activated (sensitized) T lymphocytes,

including CD4+ and CD8+ T cells (Fig. 6-19).” Id. The remainder of the text is cut off. Dr. Waters

presumably relied on this textbook excerpt to support her theory that since Menactra is T-cell

mediated it can cause this reaction. However, she provided nothing to explain how the vaccine

could cause this, or if such findings were contained in the autopsy.

Dr. Waters also submitted Yamamoto after the hearing, a case report discussing biopsy-

proven eosinophilic myocarditis related to tetanus toxoid vaccine. Pet. Ex. 28 at 1. 44 Yamamoto

noted that the endomyocardial biopsy showed “unique histopathologic findings, characterized by

perivascular eosinophilic infiltrates with myocyte necrosis and abundant interstitial lymphocytic

infiltrates with myocyte necrosis.” Id. “Immunoperoxidase staining revealed that the lymphocytic

component consisted mostly of CD3+/CD4+ T cells, suggesting a type-IV delayed hypersensitivity

reaction.” Id. The biopsy findings led to a final diagnosis of acute eosinophilic myocarditis. Id.

Yamamoto suggested that characterization of the inflammatory infiltrates in the biopsy sample

may help to identify myocarditis etiology, noting that cases of smallpox vaccine-related

myocarditis were “characterized by a prominent mixed eosinophilic and lymphocytic infiltrate.”

Id. at 4. Yamamoto further noted “another case of meningococcal C conjugate vaccine-related

myocarditis suggested a type-III hypersensitivity reaction.” Id. Yamamoto concluded that

endomyocardial biopsy is a prerequisite for diagnosis and treatment of myocarditis. Id. Notably,

while the patient in Yamamoto was suspected of having a Type-IV delayed hypersensitivity

reaction, he or she had a “prominent” mix of eosinophils and lymphocytes on biopsy and was

ultimately diagnosed with eosinophilic myocarditis rather than lymphocytic myocarditis.

Because Dr. Waters had agreed that lymphocytic myocarditis was commonly caused by a

viral infection, she was asked to reconcile how a person with evidence of only lymphocytes on

autopsy could be considered to have a clinical hypersensitivity myocarditis which requires

eosinophils. She stated that lymphocytic myocarditis is not always caused by a virus; only half of

lymphocytic myocarditis cases are viral and some of that association may be overblown because

of the sensitivity of the tests used. Tr. 80. “There’s plenty of lymphocytic myocarditis that can be

seen following a bacteria (sic) or a toxin;” 9 to 17 percent of sudden death in children is the result

of myocarditis and only 50% of those are viral. Tr. 37, 47. Therefore, half of the cases are

unaccounted for. Where there is no evidence of viral infection and another cause exists, “one would

44

Hiroyuki Yamamoto et al., A Case of Biopsy-Proven Eosinophilic Myocarditis Related to Tetanus Toxoid

Immunization, 37 CARDIOVASC. PATHOL. 54-57 (2018), filed as “Pet. Ex. 28.”

26

point to that other potential cause as the reason why we had the lymphocyte myocarditis.” Tr. 57,

84.

In Dr. Waters’ opinion, Robert fell into the 50% of lymphocytic myocarditis cases that are

not caused by viruses. Tr. 84. When asked where the 50% came from Dr. Waters stated, “that’s

just sort of general knowledge.” Tr. 84.

In her report, she relied on the “Luminex Assay results” to support her opinion that Robert

did not have a virus. See Pet. Ex. 13 at 5 (“Virology produced a negative Luminex Virus Panel

Assay, specifically influenza A, A/H1, A/H3, B; RSV A & B; Parainfluenza 1, 2, & 3; Human

Metapneumovirus; Rhinovirus and Adenovirus. Bacteriology showed negative cultures for blood

and unspecified body fluid”). At hearing, Dr. Waters was asked whether a positive result for viral

infection on the Luminex Assay would have been dispositive as the cause of Robert’s myocarditis.

Tr. 81-82. Dr. Waters responded, “It -- unless it was one of those cases where [testing] was

overdone, where there were only a few molecules seen, and it didn’t make sense clinically.” Tr.

82.

When asked whether Robert’s lymphocytic myocarditis could have been caused by his

pneumonia infection in February of 2012, Dr. Waters stated, “[C]ertainly that’s possible, but…the

studies that have done about viral infections and viral involvement with myocarditis” are “highly

sensitive…and will pick up as few as ten molecules or ten organisms.” Tr. 59. When asked if

Robert had any symptoms of a hypersensitivity myocarditis, Dr. Waters responded that Robert was

reported to be “very tired,” which could have been from myocarditis. Tr. 87.

In Dr. Waters’ opinion, Dr. Folkerth’s statement that lymphocytic myocarditis and

hypersensitivity or eosinophilic myocarditis are totally different illnesses is “solely a pathologist’s

perspective.” Pet. Ex. 13 at 6. “From a pathologist’s perspective[,] eosinophilic myocarditis has a

mixed infiltrate with a significant percentage of eosinophils, rather than the requirement that it is

primarily eosinophils.” Id. at 7. Clinically, any type of myocarditis can cause sudden death. Id. at

6. Dr. Folkerth “relies on the most common epidemiologic cause of lymphocytic myocarditis,”

viral infection, but there is no evidence in this case of a viral illness within two weeks of the

vaccination and “no support either clinically or in the autopsy for this contention.” Id. at 7. Dr.

Waters agreed with Dr. Folkerth that lymphocytic myocarditis is commonly attributed to viral

infection and the causal virus is rarely identified. Tr. 145. However, in Dr. Waters’ opinion, the

lack of eosinophils on autopsy does not rule out a hypersensitivity response to the Menactra

vaccine. Tr. 145-46.

B. Respondent’s Experts

1. Dr. Scott Yeager

i. Qualifications

Dr. Scott Yeager received a Bachelor of Arts from Dartmouth College and a medical degree

from the University of Virginia. Resp. Ex. B at 1. He completed a residency in pediatrics at the

Medical Center Hospital of Vermont and a fellowship in cardiology at the Children’s Hospital

27

Medical Center in Boston, MA. Id. He is board certified in pediatric and pediatric cardiology. Id.

at 2. Since 1985, Dr. Yeager has served as the Division Chief of Pediatric Cardiology at the

University of Vermont, where he was promoted to Professor of Pediatrics in 2012. Id. Dr. Yeager

has been involved in teaching, clinical research, and the practice of pediatric cardiology for over

30 years. Resp. Ex. A at 1. According to Dr. Yeager, he spends about 20 percent of his time on

teaching and clinical research. Tr. 153. The majority of his time, about 60 percent, is spent on his

pediatric cardiology practice; he sees between 15 and 20 patients per week, and between two and

six cases of myocarditis per year. Tr. 154. He also is the president and co-founder of the New

England Congenital Cardiology Research Foundation and co-founder of the New England

Congenital Cardiology Association. Resp. Ex. A at 1.

ii. Causation Opinion

Dr. Yeager opined that nothing in the medical literature supports Dr. Waters’ theory that

Menactra vaccine produces T-lymphocytes that can gravitate to the cardiac conduction system,

causing lymphocytic myocarditis. Tr. 162-63; Resp. Ex. E at 1. In Dr. Yeager’s opinion, Robert

died from lymphocytic myocarditis caused by a viral infection.

Dr. Yeager testified that “about 10 percent of unexpected cardiac death is associated with

myocarditis… It’s a well recognized cause of sudden death.” Tr. 175-76; Resp. Ex. A at 2-3; Resp.

Ex. A, Tab 1 at 2.45 Causes of myocarditis are variable and include 30 or more viruses, as well as

bacteria, parasites, fungi, and toxins; hypersensitivity myocarditis specifically can be caused by

drug reactions. Tr. 172. However, lymphocytic myocarditis is “almost exclusively caused by

viruses.” Tr. 176. Histologically, viral myocarditis is characterized by leukocyte infiltration,

specifically lymphocytes and macrophages, as well as evidence of myocardial injury or fibrosis.

Resp. Ex. A at 3; Resp. Ex. A, Tab 3 at 2;46 Resp. Ex. A, Tab 6 at 2.47 In his opinion as a clinician,

90 to 95% of myocarditis cases are lymphocytic. Tr. 159-60.

Dr. Yeager stated that patients with myocarditis can have variable presentations; some have

“relatively minor” symptoms, like mild chest pain, while others exhibit profound fatigue, shortness

of breath, and evidence of heart failure. Tr. 154-55. Many patients “are relatively well” but have

abnormalities on an EKG or elevated cardiac enzymes indicative of myocarditis. Tr. 154. The vast

majority of patients with myocarditis recover. Tr. 155. Biopsies of the heart are the gold standard,

but due to the associated risk, they are not typically done unless the doctors suspect the patient has

“some sort of exotic infection.” Tr. 156-57. Dr. Yeager does not see patients who are asymptomatic

because they do not show up in a clinical setting, but based on literature, he suspects that more

than 50% of people with myocarditis do not have any symptoms and that viruses affect the heart

more than is realized. Tr. 160-61. As an example, Dr. Yeager offered a study of 427 nontraumatic,

45

Christian van der Werf et al., Sudden Death in the Young: What Do We Know About It and How to

Prevent?, 3 CIRC. ARRHYTHM. ELECTROPHYSIOL. 96-104 (2010), filed as “Resp. Ex. A, Tab 1.”

46

Jared W. Magnani & G. William Dec, Myocarditis: Current Trends in Diagnosis and Treatment, 113

CIRCULATION 876-90 (2006), filed as “Resp. Ex. A, Tab 3.”

47

Heiko Mahrholdt et al., Presentation, Patterns of Myocardial Damage, and Clinical Course of Viral

Myocarditis, 114 CIRCULATION 1581-90 (2006), filed as “Resp. Ex. A, Tab 6.”

28

sudden deaths in people between the ages of 5 and 35. 11.6% of deaths were attributed to

myocarditis; half of the subjects who died of myocarditis reported a “flu-like illness.” Resp. Ex.

A, Tab 13 at 3.48 He stated therefore, “there is poor correlation between systemic viral symptoms

and myocardial involvement in lymphocytic myocarditis.” Resp. Ex. A at 3.

Dr. Yeager acknowledged that vaccines, like drugs, can cause hypersensitivity myocarditis,

which is “characterized histologically primarily by eosinophilic infiltration.” Resp. Ex. A at 3; see

also Resp. Ex. A, Tab 7 at 9.49 Dr. Yeager agreed that the smallpox vaccine can cause

hypersensitivity myocarditis but stated that he was unaware of any other vaccines that could cause

myocarditis. Tr. 166, 172, 175. To Dr. Yeager’s knowledge, the smallpox vaccine activates a

hypersensitivity reaction, resulting in eosinophilic infiltration; it is usually transient, and most

patients recover. Tr. 175. Dr. Yeager stated that a biological mechanism would need to be provided

in order for him to think that a particular vaccine could cause myocarditis. Tr. 170. When asked

whether a hypersensitivity reaction could cause sudden death, Dr. Yeager stated, “I think it

probably could…we probably don’t have enough hypersensitivity myocarditis to actually do a

study of [whether it is more or less] lethal than lymphocytic, but anything that causes inflammation

and infiltration in heart muscle can set up a fatal arrhythmia.” Tr. 176. When asked about the

pathology of a Type IV hypersensitivity reaction, Dr. Yeager deferred to the pathologists. Tr. 173-

74.

In his report, Dr. Yeager noted that there are “numerous reports of post-vaccination

myocarditis associated with vaccines, particularly with small pox vaccination.” Resp. Ex. A at 3;

Resp. Ex. A, Tab 8.50 Dr. Yeager submitted three case reports illustrating myocarditis associated

with vaccines. In Boccara, the patient developed clinical signs of hypersensitivity myocarditis four

days after receiving diphtheria, tetanus, and polio vaccinations; he was negative for viral infection

and a biopsy did not show any inflammatory infiltrate. Resp. Ex. A, Tab 9 at 1-2.51 The patient

was treated with aspirin and released within 24 hours. Id. at 2. In Dilber, the patient developed

clinical signs of hypersensitivity myocarditis three days after receiving a tetanus vaccination; the

“patient’s course was uneventful, and he was discharged on hospital day 4.” Resp. Ex. A, Tab 10

at 1-2.52 No biopsy was conducted; the type of cardiac infiltrate was not identified. In Thanjan, the

case report discussed by Dr. Chang, see supra at 17, the patient developed clinical signs of

hypersensitivity myocarditis two days after receiving DTaP, meningococcal conjugate, and

48

Rajesh Puranik et al., Sudden Death in the Young, 2 HEART RHYTHM 1277-82 (2005), filed as “Resp. Ex.

A, Tab 13.”

49

J. Butany et al., Drug-related Cardiac Pathology, 62 J. CLIN. PATHOL. 1074-84 (2009), filed as “Resp.

Ex. A, Tab 7.”

50

Dimitri C. Cassimatis et al., Smallpox Vaccination and Myopericarditis: A Clinical Review, 43 J. AM.

COLL. CARDIOL. 1503-10 (2004), filed as “Resp. Ex. A, Tab 8.”

51

Franck Boccara et al., Acute Myopericarditis After Diphtheria, Tetanus, and Polio Vaccination, 120

CHEST 671-72 (2001), filed as “Resp. Ex. A, Tab 9.”

52

Embiya Dilber et al., Acute Myocarditis Associated with Tetanus Vaccination, 78 MAYO CLIN. PROC.

1431-33 (2003), filed as “Resp. Ex. A, Tab 10.”

29

hepatitis A vaccinations. Resp. Ex. A, Tab 11 at 1.53 The patient was negative for viral infection.

Id. at 1-2. He was released four days later on an anti-inflammatory drug. Id. No biopsy was

performed, and the type of cardiac infiltrate not determined.

In Dr. Yeager’s opinion, Dr. Waters’ theory that the Menactra vaccine produced T-

lymphocytes that gravitated to the cardiac conduction system and caused Robert’s lymphocytic

myocarditis is “a concept of post-vaccination myocarditis that was unfamiliar” to him. Resp. Ex.

E at 1. Dr. Yeager explained, “…my understanding of the cardiac pathology is going to be based

on reading scientific papers by pathologists and reading textbooks by pathologists, and I have

never encountered that particular concept as a source of myocardial infiltration…. I’m not aware

of such a mechanism.” Tr. 162-63. In Dr. Yeager’s opinion “hypersensitivity myocarditis is the

generally recognized mechanism for vaccine related myocardial infiltration, and the histology in

this case does not support that diagnosis.” Resp. Ex. E at 1.

Dr. Yeager’s review of the literature found only the two case reports filed by petitioner

regarding meningococcal vaccine and myocarditis, Ball and Barton. Tr. 165. He emphasized that

both patients discussed in Barton had eosinophilic infiltration on biopsy. Resp. Ex. A at 3; Resp.

Ex. A, Tab 12 at 2-3. Overall, as a clinician, Dr. Yeager does not find case reports to be very

helpful because it is one report out of “hundreds of millions of vaccines given.” Tr. 181-82. The

number of doses of a particular vaccine administered will dictate whether you see a rare event,

because “you’re going to find pretty rare events when you’re talking that kind of volume,” and

meningococcal vaccine has had tens of millions, if not hundreds of millions, of doses administered.

Tr. 169. “If meningococcal vaccination caused myocarditis with any measurable frequency, it

would have become apparent beyond a single case report.” Resp. Ex. E at 2.

When asked about Dr. Chang’s opinion that Robert suffered from acute hypersensitivity

myocarditis, Dr. Yeager responded that it “wasn’t consistent with any pathologic model that has

ever been presented to me either in texts or in scientific papers.” Tr. 163.

In response to Dr. Chang’s opinion that Robert’s peripheral eosinophil level of 9.4% on

the day of the vaccination supported a generalized hypersensitivity reaction, Dr. Yeager stated

that, because the blood specimen was collected on the day of the vaccination, the elevated

eosinophil level could not be ascribed to the vaccine. Resp. Ex. E at 2. Robert had elevated

peripheral eosinophil levels in the past and was taking anti-convulsant medications, one of the

most common causes of peripheral eosinophilia. Id. He added a patient can have eosinophilic

infiltrate in the heart but a normal peripheral eosinophil level, or conversely, an elevated peripheral

eosinophil level with nothing in the myocardium.54 There is a weak correlation, if any, between

elevated peripheral eosinophil level and myocarditis. Tr. 165.

53

See supra n.32.

54

In Barton, Patient One had eosinophilic infiltrate on biopsy but no peripheral eosinophilia, while Patient

Two had eosinophilic infiltrate on biopsy with mild peripheral eosinophilia. Pet. Ex. 17 at 2-3; Resp. Ex.

A, Tab 12 at 2-3. In Boccara, Dilber, and Thanjan, the patients all had clinical signs of hypersensitivity

myocarditis but had peripheral eosinophil levels of 2.9, 3.0, and 3.7, respectively, all within the normal

range. See Resp. Ex. A, Tab 9 at 1; Resp. Ex. A, Tab 10 at 2; Resp. Ex. A, Tab 11 at 1.

30

Dr. Yeager pointed out that Dr. Chang did not provide any literature to support his opinion

that the absence of eosinophilic infiltrate on autopsy does not preclude a diagnosis of

hypersensitivity myocarditis, an opinion that is “in conflict with the pathologic definition.” Resp.

Ex. E at 2. Dr. Yeager further pointed out that initially Dr. Waters did not “classify this case as a

hypersensitivity myocarditis, but rather as some sort of myocardial infiltration by the vaccine-

stimulated T cells. The petitioner’s experts appear to be arguing conflicting pathologic

mechanisms.” Id.

Based on the statistics on myocarditis and sudden death, Dr. Yeager did not find anything

about Robert’s lack of symptoms or the sudden nature of his death to be inconsistent with what is

seen in otherwise healthy young adults. Tr. 176. On autopsy, Robert’s heart had “lymphocytic

inflammatory infiltrate with focal myocyte necrosis.” Resp. Ex. A at 2. There was no mention of

eosinophils, and Robert’s cause of death was determined to be lymphocytic myocarditis. Id.

Moreover, “[c]ardiac microscopy showed patchy lymphocytic infiltration, the characteristic

histologic findings of viral myocarditis….” Id. at 4. Dr. Yeager explained that “demonstrable

involvement is often patchy, as demonstrated by this case, where only one of five sampled regions

revealed active cellular infiltration.” Id. at 3. Due to sampling errors, more than 17 samples would

be necessary to correctly diagnose myocarditis in greater than 80% of cases. Id.; Resp. Ex. A, Tab

3 at 1;55 Resp. Ex. A, Tab 2.56 At hearing, Dr. Yeager was asked about the number of samples

needed “to accurately get a pathology on the heart.” Tr. 177. He explained that a larger number of

samples is needed to rule out inflammation anywhere; he added that he was unaware of any

circumstance where samples would show eosinophils in one part of the heart and lymphocytes in

another.57 Tr. 177-78. Dr. Yeager postured that “[e]osinophilic infiltration, which would be

required for a diagnosis of hypersensitivity or drug-related myocarditis, was not observed” on

Robert’s autopsy. Resp. Ex. A at 4.

Dr. Yeager agreed with the medical examiner that Robert had lymphocytic myocarditis but

conceded that he did not look at the slides because in death cases, he relies on the interpretation of

the pathologist to help him understand the underlying cause. Tr. 157-59. However, he is familiar

55

See supra n.46.

56

The authors conducted a histopathologic review of 38 cases of lymphocytic myocarditis and found that,

because lymphocytic myocarditis is generally mild, spotty, and uneven in distribution, it requires more than

the three to five samples recommended by the Dallas criteria. Resp. Ex. A, Tab 2 at 1, 9. The authors further

noted that lymphocytic myocarditis requires more samples than eosinophilic, giant cell, and granulomatous

myocarditis because the normal myocardial interstitium contains a few lymphocytes but does not contain

any of the other cell types. Id. at 10. Arthur J. Hauck et al., Evaluation of Postmortem Endomyocardial

Biopsy Specimens From 38 Patients With Lymphocytic Myocarditis: Implications for Role of Sampling

Error, 64 MAYO CLIN. PROC. 1235-45 (1989), filed as “Resp. Ex. A, Tab 2.”

57

Dr. Folkerth was put back on the stand to clarify the number of samples necessary for a histopathological

diagnosis of myocarditis. Tr. 183. She explained that the articles referred to the number of samples required

in a living patient; samples taken from a live person are much smaller than samples taken in an autopsy. Tr.

183. In this case, the five samples taken were “quite generous whole blocks of tissue, so you’re looking at

a lot more volume of tissue than you would see in biopsies.” Tr. 183. If there were eosinophils in the heart

on the autopsy in this case, they would have been picked up by the block samples taken. Tr. 183-84.

31

with the pathology of different types of myocarditis; because pathology showing eosinophils

would lead to a different course of treatment than pathology showing lymphocytes. Tr. 158-59.

Ultimately, Dr. Yeager opined that Robert died from an “almost certainly viral”

lymphocytic myocarditis which triggered a malignant ventricular arrhythmia. Resp. Ex. A at 4;

Resp. Ex. E at 3. His Menactra vaccination was “entirely unrelated” and did not contribute to his

myocarditis or sudden death “in any significant way.” Resp. Ex. A at 4; Resp. Ex. E at 3.

2. Dr. Rebecca Folkerth

i. Qualifications

Dr. Rebecca Folkerth holds a Bachelor of Science from Indiana University and a medical

degree from the University of Louisville School of Medicine. Resp. Ex. D at 1. She completed a

residency in anatomic pathology at New England Medical Center and did fellowships in pathology

and neuropathology at Harvard Medical School and Boston Children’s Hospital, respectively. Id.

Dr. Folkerth began working as a pathologist at Brigham and Women’s Hospital in 1991,

focusing on surgical pathology and neuropathology. Resp. Ex. D at 2. In 2009, she became the

director of the neuropathology division and began running the neuropathology training program

for not only Brigham and Women’s Hospital, but also Boston Children’s Hospital and Beth Israel-

Deaconess Medical Center. Id. at 3. Dr. Folkerth has also served as an associate professor of

pathology at Harvard Medical School, a consultant in pathology at Boston Children’s Hospital,

and a consultant in medical oncology at Dana-Farber Cancer Institute. Id. at 2.

Dr. Folkerth is currently a pathologist with the Chief Medical Examiner’s Office of New

York, where she primarily focuses on forensic neuropathology. Tr. 90. Her office does about 5,000

autopsies a year. Tr. 91. She autopsies the brain and nervous system for about 700 to 900 cases per

year. Tr. 91. Dr. Folkerth admitted that she is not board certified in pediatric pathology but after

28 years at Boston Children’s Hospital and her current position, which involves numerous

autopsies on children, she has significant experience in performing autopsies on children. Tr. 92.

She has been practicing for over 25 years, has performed hundreds of postmortem examinations

of adults, infants, and children, and has written over 100 peer reviewed articles and over 15

chapters for medical textbooks dealing with neuropathology. Resp. Ex. C at 2.

Dr. Folkerth has performed over 1,000 autopsies and spent 12 years as a surgical

pathologist looking at endomyocardial biopsies. Tr. 120. She has written reports where myocarditis

was the cause of death and has seen cases of myocarditis in the past year with the medical

examiner’s office. Tr. 120. She conceded that she could not recall the types of myocarditis

identified in those cases. Tr. 120. She has never personally performed an autopsy where a vaccine

was identified as the cause of death. Tr. 120. She admitted she does not know what VAERS, the

CISA network, PRISM, or Vaccine Safety Datalink are and added that she is not an epidemiologist

and does not know what a self-controlled study is. Tr. 121.

ii. Causation Opinion

32

Dr. Folkerth opined that Robert died from lymphocytic myocarditis, a condition known to

cause sudden death. Resp. Ex. C at 4. In her opinion, there was no evidence that the Menactra

vaccine played any causal role in Robert’s death. Id. at 5-6.

She explained that “Myocarditis is defined as inflammation in the myocardium,

accompanied by evidence of cell death of the cells that make up the myocardium….” Tr. 94-95.

The heart is surrounded by a membrane and an outer layer of cells called the epicardium, with a

layer of epicardial fat on the outside of the heart. Tr. 139.

Dr. Folkerth stated that her approach to examining myocarditis cases, which relies

primarily on histopathology, is consistent with the approach favored by the general scientific

community. Tr. 96-97. In her experience, and based on the literature, vaccine-associated

myocarditis has eosinophilic inflammation. Tr. 97. Dr. Chang’s suggestion that inflammation is

inflammation and the infiltrate does not matter is simplistic; the type of infiltrate identified

indicates different mechanisms. Tr. 97. Histopathologically, the infiltrate would consist of

lymphocytes, eosinophils, histiocytes, or granulomatous cells. Tr. 116.

“A lymphocyte is a type of inflammatory cell. There are multiple types of inflammatory

cells that the body produces, and each one is called to action in certain specific settings.” Tr. 93.

Lymphocytes are a marker of chronic inflammation. Tr. 140. On a slide, a lymphocyte looks like

a small, blue, round cell. Tr. 93. Eosinophils have a “very distinctive appearance…completely

different from lymphocytes…. So it’s quite easy to tell them apart on a slide or even in peripheral

blood.” Tr. 93-94. “There’s no way you would confuse an eosinophilic infiltrate with a

lymphocytic infiltrate.” Tr. 96. Though there may be mixed infiltrates, the “presence of eosinophils

at all would lead you to a sensitivity, and the hypersensitivity or allergic type [of myocarditis].

And the absence of eosinophils would lead you away from that diagnosis.” Tr. 96; Resp. Ex. F at

1 (“[E]osinophilic refers to the type of inflammatory cell associated with hypersensitivity (allergic

type) reactions…whereas lymphocytic refers to inflammation almost certainly related…to viral

infection.”) (emphasis omitted).

Dr. Folkerth explained that the pattern of inflammation on Robert’s heart and the presence

of lymphocytes is evidence of viral myocarditis. Tr. 108-09. The most common cause of

lymphocytic myocarditis is viral infection, which was most likely the cause of death in this case,

“even though studies to detect the most common viruses (Coxsackie [enterovirus], adenovirus,

herpes virus type 6, or parvovirus B19) were not available.” Resp. Ex. C at 5. Dr. Folkerth noted

that, if the paraffin blocks containing the tissue samples still exist, they could be sent to the CDC

for viral testing.58 Tr. 142. However, “the inability to identify a particular virus is the usual clinical

situation and does NOT (sic) decrease the likelihood” that a virus caused Robert’s lymphocytic

myocarditis. Resp. Ex. F at 1; Tr. 100-01, 107-08. “[I]t’s the usual situation that someone can be

infected and not know it and have a sudden cardiac death.” Tr. 109. She agreed with the autopsy

report’s conclusion that Robert suffered from lymphocytic myocarditis based on the presence of

lymphocytic inflammation in the myocardium. Tr. 98. “It’s pretty clear-cut what happened here. I

think it was the viral myocarditis, and it was fatal, and it was asymptomatic, as they often are.” Tr.

112. She further noted that the heart tissue showed inflammation in the epicardial fat; in Dr.

Folkerth’s opinion, this is a marker for the degree of the severity of inflammation. Tr. 139-140.

58

Petitioner filed a status report on April 2, 2018, advising that the paraffin blocks no longer exist.

33

“That type of inflammation takes some days to weeks to develop. That’s not an acute type of

reaction.” Tr. 140.

In her report, Dr. Folkerth stated, “While one cannot absolutely exclude the possibility that

Robert succumbed to an immunologic reaction related to vaccination, this is not likely given the

much higher prevalence of viral myocarditis and its known propensity to precipitate sudden death.”

Resp. Ex. C at 5. Epidemiology favors lymphocytic myocarditis rather than an unrelated single

second dose of vaccination Robert received three days prior to his death. Id. When asked about

this statement at hearing, Dr. Folkerth stated that “anything is possible,” but a reaction to a

Menactra vaccine would not be consistent with the pattern of inflammation seen on autopsy in this

case. Tr. 117-19. In an experimental animal model, you could “give it a vaccine and cause

this…it’s possible, but I wouldn’t call it biologically plausible.” Tr. 119. Based on all of the

evidence available, the most likely series of events is that Robert developed lymphocytic

myocarditis caused by a virus. Tr. 117.

Dr. Folkerth explained that “the Menactra vaccine is generated from some of the sugars

that are on the outside capsule of the meningococcus bacterium,” and those sugars are then stuck

to a separate unrelated protein. Tr. 113. When the vaccine is injected, it “causes the body to develop

lymphocytes that will then recognize that combination of sugars as being meningococcus. So then

if the person is later exposed to meningococcus, the T-cells will go and kill the bacterium….” Tr.

113.

Dr. Folkerth agreed that T-lymphocytes would be produced as a typical immune response

to the Menactra vaccine or any other “offending organism” including actual meningococcal

bacteria. Tr. 135-37. However, there is no pathophysiological support for Dr. Waters’ opinion that

the T-lymphocytes produced in response to the Menactra vaccine gravitated to the heart or that the

vaccine is analogous to actual live meningococcal bacteria. Tr. 112.

Dr. Folkerth agreed with Dr. Waters’ explanation of Type I and Type IV hypersensitivity

reactions. Tr. 125. However, Dr. Folkerth added that an analysis of Type I vs. Type IV

hypersensitivity is an immunologic textbook type of explanation that is not practical in terms of

histopathology and is not the terminology used on a daily basis when examining tissue. Tr. 100. A

practical analysis focuses on whether the type of cell present is an eosinophil, lymphocyte, or

histiocytic granuloma. Tr. 100.

Dr. Folkerth also agreed that a person could have simultaneous Type I and Type IV

reactions but did not agree with Dr. Waters that one could have a Type I reaction and later a Type

IV reaction. Tr. 125-26. Dr. Folkerth agreed with Dr. Waters that, in order to prove this was

possible, a patient would have to undergo constant endomyocardial biopsies over several weeks,

which would be unethical. Tr. 125-26. Dr. Folkerth disagreed with Dr. Waters’ suggestion that

there were eosinophils first that disappeared, leaving only lymphocytes; proving that would also

require several biopsies, and is not consistent with the literature on Type I and Type IV reactions.

Tr. 126. Dr. Folkerth agreed that a hypersensitivity myocarditis could have the presence of

lymphocytes with eosinophils but not lymphocytes alone. Tr. 99-100.

34

Dr. Folkerth further agreed that Menactra could cause an allergic reaction, hypersensitivity

response, or eosinophilic response in a sensitive person. Tr. 128-31. An acute hypersensitivity

response, like an asthma attack, can take minutes to hours. Tr. 131-32. A hypersensitivity response

that takes days would be a Type IV response. Tr. 132. Dr. Folkerth admitted that she did not know

how long it would take for eosinophils to be seen in the heart following a Type I hypersensitivity

response but noted that eosinophils can be seen in tissue relatively quickly after exposure. Tr. 132-

34. For example, eosinophils can be seen in the trachea tissue of a person who dies from an asthma

attack, even though the death would occur less than an hour after exposure. Tr. 132-33.

When asked whether it was possible to see an elevated level of eosinophils in peripheral

blood after receiving a Menactra vaccination, Dr. Folkerth admitted that she did not know. Tr.

126-27. However, Dr. Folkerth explained, Robert’s elevated peripheral eosinophil level of 9.4%

is not very helpful because “unless you had a blood draw taken before he received the vaccine,

showing that it was below nine, there’s no way you can say that the vaccine caused it to go up. He

could have had that eosinophil count walking into the doctor’s office and very likely did.” 59 Tr.

127. She noted that Robert’s previous eosinophil level was six, which is “on the high side” of

normal; he was also on “medications that are known to cause peripheral eosinophilia….” Tr. 127-

28. Dr. Folkerth added, “you can have an eosinophilic infiltrate in tissue and have a normal blood

eosinophil count and vice versa. They are not necessarily correlated.” Tr. 128. When asked why

she did not mention Robert’s antiseizure medication as a possible cause of his myocarditis, Dr.

Folkerth explained that, if the medications had caused a hypersensitivity response, Robert would

have had eosinophilic infiltrate in the heart instead of lymphocytic infiltrate. Tr. 113.

In response to Dr. Chang’s opinion that Robert suffered from hypersensitivity myocarditis,

Dr. Folkerth cited to several articles which describe the characteristics of different types of

myocarditis, specifically distinguishing hypersensitivity myocarditis from lymphocytic

myocarditis. Resp. Ex. C at 5; Resp. Ex. C, Tab 1 at 1 (“Numerous medications…can induce

hypersensitivity eosinophilic myocarditis, which commonly is reversible after withdrawal of the

causative agent”);60 Resp. Ex. C, Tab 2 at 5 (Characterizing myocarditis associated with drugs or

vaccines as “hypersensitivity eosinophilic myocarditis”);61 Resp. Ex. C, Tab 3 at 1 (“In general,

the histologic patterns of myocarditis are categorized by the predominant inflammatory cells and

can be divided into lymphocytic (including viral and autoimmune forms)…eosinophilic

(hypersensitivity myocarditis or hypereosinophilic syndrome….”).62 Dr. Folkerth also rejected Dr.

Chang’s comparison of this case to the patient in Thanjan.63 Resp. Ex. C at 5. Dr. Folkerth pointed

59

It was never established whether Robert’s blood work was done before or after he received the Menactra

vaccine. Petitioner’s experts made assumptions without evidence in the record. However, the literature does

not support a correlation between peripheral eosinophils and eosinophilic infiltrate in the tissue.

60

Ingrid Kindermann et al., Update on Myocarditis, 59 J. AM. COLL. CARDIOL. 779-92 (2012), filed as

“Resp. Ex. C, Tab 1.”

61

Sandeep Sagar et al., Myocarditis, 379 LANCET 738-47 (2011), filed as “Resp. Ex. C, Tab 2.”

62

Ayelet Shauer et al., Acute Viral Myocarditis: Current Concepts in Diagnosis and Treatment, 15 ISR.

MED. ASSOC. J. 180-85 (2013), filed as “Resp. Ex. C, Tab 3.”

63

See supra n.32.

35

out that the adolescent in Thanjan received multiple vaccinations, developed arthralgia and chest

pain, and was diagnosed with hypersensitivity myocarditis based on elevated cardiac enzymes,

abnormal ECG, and negative viral studies. Id. Notably, the patient in Thanjan did not undergo

endomyocardial biopsy. Id. After the hearing, Dr. Folkerth responded to the Yamamoto case report

submitted by petitioner, stating that it was not relevant to this matter because Yamamoto dealt with

biopsy-proven eosinophilic myocarditis following a tetanus vaccination. Resp. Ex. F; Pet. Ex. 28.

She added that eosinophilic myocarditis is a completely different type of heart inflammation than

lymphocytic myocarditis, which is what Robert had.

V. Applicable Law

A. Legal Standard Regarding Causation

The Vaccine Act provides two avenues for petitioners to receive compensation. First, a

petitioner may demonstrate a “Table” injury—i.e., an injury listed on the Vaccine Injury Table

that occurred within the provided time period. § 11(c)(1)(C)(i). “In such a case, causation is

presumed.” Capizzano v. Sec’y of Health & Human Servs., 440 F.3d 1317, 1320 (Fed. Cir. 2006);

see § 13(a)(1)(B). Second, where the alleged injury is not listed on the Vaccine Injury Table, a

petitioner may demonstrate an “off-Table” injury, which requires that the petitioner “prove by a

preponderance of the evidence that the vaccine at issue caused the injury.” Capizzano, 440 F.3d at

1320; see § 11(c)(1)(C)(ii). Initially, a petitioner must provide evidence that he or she suffered, or

continues to suffer, from a definitive injury. Broekelschen v. Sec’y of Health & Human Servs., 618

F.3d 1339, 1346 (Fed. Cir. 2010). A petitioner need not show that the vaccination was the sole

cause, or even the predominant cause, of the alleged injury; showing that the vaccination was a

“substantial factor” and a “but for” cause of the injury is sufficient for recovery. See Pafford v.

Sec’y of Health & Human Servs., 451 F.3d 1352, 1355 (Fed. Cir. 2006); Shyface v. Sec’y of Health

& Human Servs., 165 F.3d 1344, 1352 (Fed. Cir. 1999).64

To prove causation for an “off-Table” injury, petitioners must satisfy the three-pronged test

established in Althen v. Sec’y of Health & Human Servs., 418 F.3d 1274 (Fed. Cir. 2005). Althen

requires that petitioners show by preponderant evidence that a vaccination petitioner received

caused his or her injury “by providing: (1) a medical theory causally connecting the vaccination

and the injury; (2) a logical sequence of cause and effect showing that the vaccination was the

reason for the injury; and (3) a showing of a proximate temporal relationship between vaccination

and injury.” Id. at 1278. Together, these prongs must show “that the vaccine was ‘not only a but-

for cause of the injury but also a substantial factor in bringing about the injury.’” Stone v. Sec’y of

Health & Human Servs., 676 F.3d 1373, 1379 (Fed. Cir. 2012) (quoting Shyface, 165 F.3d at 1352-

53). Causation is determined on a case-by-case basis, with “no hard and fast per se scientific or

medical rules.” Knudsen v. Sec’y of Health & Human Servs., 35 F.3d 543, 548 (Fed. Cir. 1994).

Petitioners are not required to identify “specific biological mechanisms” to establish causation,

nor are they required to present “epidemiologic studies, rechallenge, the presence of pathological

64

The Vaccine Act also requires petitioners to show by preponderant evidence the vaccinee suffered from

the “residual effects or complications” of the alleged vaccine-related injury for more than six months, died

from the alleged vaccine-related injury, or required inpatient hospitalization and surgical intervention as a

result of the alleged vaccine-related injury. § 11(c)(1)(D). It is undisputed that this requirement is satisfied

in this case.

36

markers or genetic disposition, or general acceptance in the scientific or medical communities.”

Capizzano, 440 F.3d at 1325 (quoting Althen, 418 F.3d at 1280). “[C]lose calls regarding causation

are resolved in favor of injured claimants.” Althen, 418 F.3d at 1280.

Each of the Althen prongs requires a different showing. The first Althen prong requires

petitioner to provide a “reputable medical theory” demonstrating that the vaccines received can

cause the type of injury alleged. Pafford, 451 F.3d at 1355-56 (citation omitted). To satisfy this

prong, petitioner’s “theory of causation must be supported by a ‘reputable medical or scientific

explanation.’” Andreu ex rel. Andreu v. Sec’y of Health & Human Servs., 569 F.3d 1367, 1379

(Fed. Cir. 2009) (quoting Althen, 418 F.3d at 1278). This theory need only be “legally probable,

not medically or scientifically certain.” Id. at 1380 (emphasis omitted) (quoting Knudsen, 35 F.3d

at 548). Nevertheless, “petitioners [must] proffer trustworthy testimony from experts who can find

support for their theories in medical literature.” LaLonde v. Sec’y of Health & Human Servs., 746

F.3d 1334, 1341 (Fed. Cir. 2014).

The second Althen prong requires proof of a “logical sequence of cause and effect.”

Capizzano, 440 F.3d at 1326 (quoting Althen, 418 F.3d at 1278). In other words, even if the

vaccinations can cause the injury, petitioner must show “that it did so in [this] particular case.”

Hodges v. Sec’y of Health & Human Servs., 9 F.3d 958, 962 n.4 (Fed. Cir. 1993) (citation omitted).

“A reputable medical or scientific explanation must support this logical sequence of cause and

effect,” id. at 961 (citation omitted), and “treating physicians are likely to be in the best position

to determine whether a logical sequence of cause and effect show[s] that the vaccination was the

reason for the injury,” Paluck v. Sec’y of Health & Human Servs., 786 F.3d 1373, 1385 (Fed. Cir.

2015) (quoting Andreu, 569 F.3d at 1375). Petitioner is not, however, required “to eliminate

alternative causes as part of establishing [their] prima facie case.” Doe v. Sec’y of Health & Human

Servs., 601 F.3d 1349, 1357-58 (Fed. Cir. 2010); see Walther v. Sec’y of Health & Human Servs.,

485 F.3d 1146, 1152 (Fed. Cir. 2007) (holding that a “petitioner does not bear the burden of

eliminating alternative independent potential causes”).

To satisfy the third Althen prong, petitioner must establish a “proximate temporal

relationship” between the vaccination and the alleged injury. Althen, 418 F.3d at 1281. This

“requires preponderant proof that the onset of symptoms occurred within a timeframe for which,

given the medical understanding of the disorder’s etiology, it is medically acceptable to infer

causation-in-fact.” De Bazan v. Sec’y of Health & Human Servs., 539 F.3d 1347, 1352 (Fed. Cir.

2008). Typically, “a petitioner’s failure to satisfy the proximate temporal relationship prong is due

to the fact that onset was too late after the administration of a vaccine for the vaccine to be the

cause.” Id. However, “cases in which onset is too soon” also fail this prong; “in either case, the

temporal relationship is not such that it is medically acceptable to conclude that the vaccination

and the injury are causally linked.” Id.; see also Locane v. Sec’y of Health & Human Servs., 685

F.3d 1375, 1381 (Fed. Cir. 2012) (“[If] the illness was present before the vaccine was administered,

logically, the vaccine could not have caused the illness.”).

B. Legal Standard Regarding Fact Finding

The process for making factual determinations in Vaccine Program cases begins with

analyzing the medical records, which are required to be filed with the petition. § 11(c)(2). Medical

37

records created contemporaneously with the events they describe are presumed to be accurate and

“complete” such that they present all relevant information on a patient’s health problems. Cucuras

v. Sec’y of Health & Human Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993). In making

contemporaneous reports, “accuracy has an extra premium” given that the “proper treatment

hang[s] in the balance.” Id. Contemporaneous medical records that are clear, consistent, and

complete warrant substantial weight “as trustworthy evidence.” Id. Indeed, “where later testimony

conflicts with earlier contemporaneous documents, courts generally give the contemporaneous

documentation more weight.” Campbell ex rel. Campbell v. Sec’y of Health & Human Servs., 69

Fed. Cl. 775, 779 (2006); see United States v. U.S. Gypsum Co., 333 U.S. 364, 396 (1948). But

petitioners can support their claim with oral testimony if it is credible and consistent with the

medical records. See, e.g., Stevenson ex rel. Stevenson v. Sec’y of Health & Human Servs., No. 90-

2127V, 1994 WL 808592, at *7 (Fed. Cl. Spec. Mstr. June 27, 1994) (crediting the testimony of a

fact witness whose “memory was sound” and “recollections were consistent with the other factual

evidence”). In short, “the record as a whole” must be considered. § 13(a).

C. Evaluating Expert Testimony

Establishing a sound and reliable medical theory connecting the vaccine to the injury often

requires a petitioner to present expert testimony in support of his or her claim. Lampe v. Sec’y of

Health & Human Servs., 219 F.3d 1357, 1361 (Fed. Cir. 2000). The Supreme Court’s opinion in

Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993), requires that courts

determine the reliability of an expert opinion before it may be considered as evidence. “In short,

the requirement that an expert’s testimony pertain to ‘scientific knowledge’ establishes a standard

of evidentiary reliability.” Id. at 590 (citation omitted). Thus, for Vaccine Act claims, a “special

master is entitled to require some indicia of reliability to support the assertion of the expert

witness.” Moberly ex rel. Moberly v. Sec’y of Health & Human Servs., 592 F.3d 1315, 1324 (Fed.

Cir. 2010). The Daubert factors are used in the weighing of the reliability of scientific evidence

proffered. Davis v. Sec’y of Health & Human Servs., 94 Fed. Cl. 53, 66-67 (2010) (“uniquely in

this Circuit, the Daubert factors have been employed also as an acceptable evidentiary-gauging

tool with respect to persuasiveness of expert testimony already admitted”). Where both sides offer

expert testimony, a special master’s decision may be “based on the credibility of the experts and

the relative persuasiveness of their competing theories.” Broekelschen, 618 F.3d at 1347 (citing

Lampe, 219 F.3d at 1362). And nothing requires the acceptance of an expert’s conclusion

“connected to existing data only by the ipse dixit of the expert,” especially if “there is simply too

great an analytical gap between the data and the opinion proffered.” Snyder ex rel. Snyder v. Sec’y

of Health & Human Servs., 88 Fed. Cl. 706, 743 (2009) (quoting Gen. Elec. Co. v. Joiner, 522

U.S. 136, 146 (1997)).

D. Consideration of Medical Literature

Finally, although this decision discusses some but not all of the literature in detail, the

undersigned reviewed and considered all of the medical records and literature submitted in this

matter. See Moriarty ex rel. Moriarty v. Sec’y of Health & Human Servs., 844 F.3d 1322, 1328

(Fed. Cir. 2016) (“We generally presume that a special master considered the relevant record

evidence even though [s]he does not explicitly reference such evidence in h[er] decision.”);

Simanski v. Sec’y of Health & Human Servs., 115 Fed. Cl. 407, 436 (2014) (“[A] Special Master

38

is ‘not required to discuss every piece of evidence or testimony in her decision.’” (citation

omitted)), aff’d, 601 F. App’x 982 (Fed. Cir. 2015).

VI. Analysis

Because petitioner does not allege an injury listed on the Vaccine Injury Table, her claim

is classified as “off-Table.” As noted above, for petitioner to prevail on an “off-Table” claim, she

must show by preponderant evidence that Robert’s injury resulted from the vaccination at issue.

Capizzano, 440 F.3d at 1320. Doing so shifts the burden to respondent to show that the injury was

caused by factors unrelated to the vaccinations. Deribeaux ex rel. Deribeaux v. Sec’y of Health &

Human Servs., 717 F.3d 1363, 1367 (Fed. Cir. 2013).

A. Overview of Myocarditis

Myocarditis is an inflammation of the muscular walls of the heart. DORLAND’S at 1222.

Myocarditis can be difficult to diagnose because it has a wide variety of causes and clinical

presentations. Resp. Ex. A, Tab 3 at 1.65 Myocarditis is classified into types based on

histopathology. “Active myocarditis is characterized by an inflammatory cellular infiltrate with

evidence of myocyte necrosis.” Id. The inflammatory infiltrate can be described as lymphocytic,

eosinophilic, or granulomatous. Id. “The amount of inflammation may be mild, moderate, or

severe, and its distribution may be focal, confluent, or diffuse, respectively.” Id.

Lymphocytic myocarditis accounts for the majority of myocarditis cases. Resp. Ex. A, Tab

5 at 1. Enteroviruses, specifically coxsackie group A and B, are traditionally the predominant viral

cause, but myocarditis can be caused by a variety of viruses, including influenza A and B,

adenovirus, Epstein-Barr virus, herpes viruses, cytomegalovirus, yellow fever, and retroviruses.

Resp. Ex. A, Tab 3 at 1; Resp. Ex. A, Tab 5 at 3-4;66 Resp. Ex. A, Tab 6 at 1;67 Pet. Ex. 18 at 4.68

Bacterial infections, including Neisseria meningitidis, beta-hemolytic streptococci, diphtheria, and

Borrelia burgdorferi, have been implicated in bacterial myocarditis. Pet. Ex. 18 at 4. “Advances

in molecular techniques have demonstrated the presence of viral genome in the myocardium of a

significant percentage of patients presenting with unexplained dilated cardiomyopathy….” Resp.

Ex. A, Tab 3 at 1. These “techniques have substantiated the long-held perception that viral

infection plays a key role in the development of active myocarditis.” Id. at 2. In addition to

enterovirus, hepatitis C virus has been reported in Japanese patients and parvovirus B19 in German

patients. Id.

The pathogenesis for lymphocytic myocarditis is believed to be direct myocardial invasion

65

See supra n.46.

66

Neil E. Bowles et al., Detection of Viruses in Myocardial Tissues by Polymerase Chain Reaction:

Evidence of Adenovirus as a Common Cause of Myocarditis in Children and Adults, 42 J. AM. COLL.

CARDIOL. 466-72 (2003), filed as “Resp. Ex. A, Tab 5.”

67

See supra n.47.

68

See supra n.37.

39

by cardiotropic virus or other infectious agents which rapidly progresses to a second phase of

immunologic activation. Resp. Ex. A, Tab 3 at 3. In the last phase, CD4+ activation prompts clonal

expansion of B cells, resulting in further myocytolysis,69 additional local inflammation, and

production of circulating anti-heart antibodies. Id. All three mechanisms may interact within the

same host; the predominant pathogenic mechanism may vary according to host defenses and the

specific infectious agent. Id. at 3-4. Clinical manifestations can range from no symptoms at all to

cardiogenic shock, but the majority of patients are asymptomatic. Id. at 4; Resp. Ex. A, Tab 4 at

3.70

Endomyocardial biopsy, or taking tissue samples of the heart, is the gold standard for

diagnosing myocarditis. Resp. Ex. A, Tab 4 at 6. Autopsy sampling of the heart is more extensive.

Eosinophilic, or hypersensitivity, myocarditis is characterized by eosinophilic infiltration,

the degree of which depends on the underlying condition and the degree and duration of

eosinophilic exposure. Pet. Ex. 25 at 1.71 Eosinophilic myocarditis is associated with

hypersensitivity reactions, immune-mediated disorders, infections, cancer, vaccines, and

numerous medications including antidepressants, antibiotics, and antipsychotics. Id. at 1, 7. One

case of eosinophilic myocarditis following smallpox vaccine has been confirmed by

endomyocardial biopsy. Resp. Ex. A, Tab 3 at 3. In a large number of cases, however, the

underlying cause is unknown. Pet. Ex. 25 at 1. The clinical presentation can vary widely, ranging

from nonspecific symptoms of fever, dyspnea, and chest pain to peripheral blood eosinophilia,

sinus tachycardia, and rash, to an acute fulminant necrotizing myocarditis or chronic restrictive

cardiomyopathy that rapidly results in cardiovascular deterioration and circulatory collapse. Pet.

Ex. 25 at 1, 3-5; Resp. Ex. A, Tab 3 at 3.

Eosinophilic myocarditis is most often fatal and discovered on autopsy. Pet. Ex. 25 at 2. A

poor correlation exists between the degree of myocardial inflammation or necrosis and the

likelihood of arrhythmias or hemodynamic collapse. Resp. Ex. A, Tab 3 at 3.

In what appears to be the largest study of eosinophilic myocarditis based on a series of

published cases, Brambatti et. al. noted that hypersensitivity was the most frequently reported

presentation of eosinophilic myocarditis. Pet. Ex. 25 at 4. Drugs most frequently associated with

hypersensitivity eosinophilic myocarditis were antibiotics, central nervous system agents,

vaccines, antitubercular agents, and other agents. Id. at 7-8. No specific vaccines were noted.

Cessation of the offending drug was thought to be the most effective treatment. Id. at 12.

Pathological findings showed that, in hypersensitivity eosinophilic myocarditis, eosinophilic

myocardial infiltrates range from mild to severe, but did not correlate with the incidence of death

or the levels of peripheral eosinophilia. Id. Furthermore, eosinophilic myocarditis often has a

fulminant presentation with abrupt impairment of left ventricle ejection fraction and high risk of

69

Myocytolysis is the disintegration of muscle fibers. Myocytolysis, DORLAND’S at 1222.

70

Laurent Andreoletti et al., Viral Causes of Human Myocarditis, 102 ARCH. CARDIOVASC. DIS. 559-68

(2009), filed as “Resp. Ex. A, Tab 4.”

71

See supra n.42.

40

malignant arrhythmias. Id.

B. The Menactra Vaccine

Meningococcal disease is caused by Neisseria meningitidis bacteria. Pet. Ex. 27 at 1.72 It

is a serious bacterial illness that can lead to meningitis,73 bacterial pneumonia, or bacteremia. Id.

The bacterium has an inner and outer membrane; the outer membrane is surrounded by a

polysaccharide capsule. Id. Meningococcal strains are classified based on the structure of this

polysaccharide capsule. Id. Thirteen strains have been identified, but “[a]lmost all invasive disease

is caused by one of five serogroups: A, B, C, W, and Y.” Id. at 1-2.

Menactra “contains N. meningitidis serogroup A, C, Y, and W-135 capsular polysaccharide

antigens individually conjugated to diphtheria toxoid protein.” Pet. Ex. 26 at 25. The

polysaccharides and the protein are purified and detoxified. Id. No preservative or adjuvant is

added during manufacture. Id.; Pet. Ex. 27 at 6 (Menactra “does not contain a preservative or an

adjuvant”). “An advantage of conjugate vaccines is their ability to elicit immunologic memory.

Meningococcal conjugate vaccines prime the immune system, and immunologic memory persists

even in the absence of detectible bactericidal antibodies.” Pet. Ex. 27 at 8.

C. Petitioner Has Not Carried Her Burden of Proof

The experts agreed that Robert had myocarditis which caused his death. The experts also

agreed that Robert had no symptoms of any viral illness in the weeks preceding his death. The

experts disagree on the cause of Robert’s myocarditis. Petitioner’s expert Dr. Chang opined that

Robert had a hypersensitivity myocarditis caused by the Menactra vaccine which ultimately lead

to cardiac collapse. Dr. Waters opined that that Menactra vaccine is a T-lymphocyte mediated

vaccine and therefore, the vaccine caused lymphocytic myocarditis which resulted in Robert’s

cardiac collapse and death; he may have also had a hypersensitivity reaction. Respondent’s experts,

Drs. Yeager and Folkerth, opined that Robert had lymphocytic myocarditis caused by viral

infection which often goes undetected, is asymptomatic, and can cause sudden death; the Menactra

vaccine had nothing to do with it and was merely temporally associated, which is of no

consequence. Nothing in the autopsy suggests that Robert had a hypersensitivity or allergic

myocarditis, as no eosinophils were found in the heart.

The Luminex Virus Assay Panel was a source of contention in this case. Dr. Folkerth

admitted that she mistakenly made a reference in her report to a Luminex Virus Assay Panel with

negative results for the viruses tested. Petitioner argued vehemently at hearing, and again during a

status conference thereafter, that Dr. Folkerth’s testimony should be stricken in its entirety as a

result of this mistake. However, it was only petitioner’s experts, neither of whom admittedly ever

looked for the actual test or results, who relied solely on Dr. Folkerth’s report as a basis for their

opinions that the vaccine caused Robert’s lymphocytic myocarditis and ultimate death because no

72

CENTERS FOR DISEASE CONTROL AND PREVENTION, EPIDEMIOLOGY AND PREVENTION OF VACCINE-

PREVENTABLE DISEASES 231-46 (Jennifer Hamborksy et al. eds., 13th ed. 2015), filed as “Pet. Ex. 27.”

73

Meningitis is an inflammation of the meninges, the three membranes that envelope the brain and spinal

cord. Meningitis, DORLAND’S at 1132; meninges, id.

41

viral infection was ever found. Pet. Ex. 13 at 5; Pet. Ex. 11 at 4.

1. The Preponderance of the Evidence Indicates that Robert Suffered from

Lymphocytic Myocarditis

The Federal Circuit has determined that if there is a dispute as to the nature of a vaccinee’s

injury, the special master may opine on the nature of said injury. Contreras v. Sec’y of Health &

Human Servs., 844 F.3d 1363, 1368 (Fed. Cir. 2017), citing Hibbard v. Sec’y of Health & Human

Servs., 698 F.3d 1355, 1365 (Fed. Cir. 2012).

As discussed above, a key dispute in this matter is whether Robert suffered from

lymphocytic or eosinophilic myocarditis. In her pre-hearing brief and at hearing, petitioner took

the position that Robert suffered lymphocytic myocarditis; however, in her post-hearing brief,

petitioner argued that Robert had eosinophilic myocarditis. See Pet. Ex. 13 at 7; Pet. Brief at 7;

Pet. Post-Hearing Brief at 6. Respondent maintained throughout the pendency of this matter that

Robert suffered from lymphocytic myocarditis. See Resp. Brief at 3; Resp. Post-Hearing Brief at

1-2. The autopsy found the cause of death to be lymphocytic myocarditis. Pet. Ex. 3 at 10.

Drs. Chang, Waters, Folkerth, and Yeager agreed that Robert’s autopsy showed

lymphocytic infiltrate in the heart tissue, histopathological evidence of lymphocytic myocarditis,

and no evidence of eosinophilic infiltrate in the heart tissue. Tr. 69, 70, 98, 108-09, 113, 126, 157-

59, 206, 208; Resp. Ex. A at 2, 4. Drs. Waters, Yeager, and Folkerth agreed that absence of

eosinophils on biopsy would preclude a diagnosis of eosinophilic myocarditis. Tr. 99-100, 149-

50; Resp. Ex. A at 4. Dr. Chang only commented on the relationship of eosinophilic infiltrate to

hypersensitivity myocarditis, opining that hypersensitivity myocarditis could be characterized by

either eosinophils or lymphocytes. Tr. 190-91, 194, 204-05, 224; Pet. Ex. 11 at 4. Dr. Yeager

pointed out that Dr. Chang did not support this opinion with any literature. Resp. Ex. E at 2.

Petitioner submitted that, despite the lack of eosinophilic infiltrate in the heart, the elevated

level of peripheral eosinophils is sufficient for a showing of eosinophilic myocarditis. See Pet.

Post-Hearing Brief at 6. Both Dr. Chang and Dr. Waters pointed to the peripheral eosinophilia as

evidence of a hypersensitivity reaction. Tr. 36, 51-52, 54, 192-93; Pet. Ex. 11 at 4. Drs. Yeager

and Folkerth provided evidence that there is a weak correlation between peripheral eosinophilia

and eosinophilic myocarditis. Tr. 128, 165. According to respondent’s experts, a person can have

eosinophilic myocarditis without elevated peripheral eosinophils, or elevated peripheral

eosinophils without eosinophilic myocarditis. Tr. 128, 165. Literature submitted by respondent

supports the lack of correlation. See Resp. Ex. A, Tab 12 at 374 (“…patients with eosinophilic

myocarditis resulting from hypersensitivity have mildly elevated or normal eosinophil counts”);

Resp. Ex. C, Tab 2 at 575 (“Hypersensitivity myocarditis is particularly difficult to recognize

because the clinical features characteristic of a drug hypersensitivity reaction—including non-

specific skin rash, malaise, fever, and eosinophilia—are absent in most cases”). Respondent’s

experts also noted that Robert’s anti-seizure medications could have caused elevated peripheral

eosinophil levels, see Tr. 141, 164, Resp. Ex. E at 2, including Robert’s previously elevated

74

See supra n.40.

75

See supra n. 61.

42

peripheral eosinophil levels of 6.0 and 7.2 on January 23, 2012 and February 11, 2011,

respectively. See Pet. Ex. 1 at 58; Pet. Ex. 2.2 at 21. Petitioner’s experts agreed that Robert’s anti-

seizure medications could have contributed to his elevated eosinophil levels but opined that the

medications would not have caused “an acute increase” on the same day that Robert received the

Menactra vaccine. Tr. 60-61, 199. However, as Dr. Folkerth pointed out, the medical records do

not indicate whether Robert’s blood work was taken before or after he received the Menactra

vaccine, so he could have arrived at Dr. Barsh’s office with an elevated eosinophil level of 9.0. Tr.

127.

The literature submitted by both parties overwhelmingly supports endomyocardial biopsy

as the “gold standard” in diagnosing myocarditis; essentially, the biopsy results are the

determinative factor in whether a patient has myocarditis, and if so, the type of myocarditis. See,

e.g., Resp. Ex. A, Tab 3 at 5 (“EMB findings remain the gold standard for unequivocally

establishing the diagnosis.”); Resp. Ex. A, Tab 4 at 9 (“…the analysis of EMB is the gold standard

for establishing the diagnosis unequivocally…”); Resp. Ex. C, Tab 1 at 1 (“Endomyocardial biopsy

remains the gold standard for in vivo diagnosis of myocarditis.”); Resp. Ex. C, Tab 2 at 6

(“Histological or immunohistological evidence of an inflammatory cell infiltrate with or without

myocyte damage is the gold standard for the diagnosis of myocarditis”).

Petitioner further submitted that, without evidence that Robert had a viral infection, the

tissue samples showing lymphocytic infiltrate in the heart is insufficient for a diagnosis of

lymphocytic myocarditis. Pet. Post-Hearing Brief at 4. It was established after lengthy discussion

during the hearing that the Luminex Virus Assay Panel, which was purportedly negative for viral

infection, was never conducted. Tr. 41-44, 101-06. Accordingly, it is unknown whether Robert

was suffering from a viral infection at the time of his death. The experts agreed that lymphocytic

myocarditis is most commonly caused by viruses. Tr. 47, 80, 99, 159-60, 176, 213; Pet. Ex. 13 at

6; Resp. Ex. A at 3; Resp. Ex. C at 5. However, Dr. Waters opined that Robert fell into the 50%

of myocarditis cases that are not caused by viruses. Tr. 84. She could not however provide support

for this statistic. Further, she stated, “I’ve heard that Robert was very tired” in the days following

his vaccination, “and he could have been tired because he had some myocarditis,” but could not

explain why fatigue would not also be a symptom of a viral infection. Tr. 87.

The petitioner has the burden of proving, by a preponderance of the evidence, that the

vaccinee actually suffered from the injury which they are alleging was caused by the vaccine. See

Hibbard, 698 F.3d at 1365. The record is replete with support for the primacy of endomyocardial

biopsy results in determining a diagnosis of myocarditis. Petitioner has not refuted this support,

nor has she provided literature to support her argument that peripheral eosinophilia, absent

eosinophilic infiltrate on biopsy, is sufficient for a diagnosis of eosinophilic myocarditis. Robert’s

heart tissue showed lymphocytic infiltrate alone. The autopsy concluded his death was from

lymphocytic myocarditis. The opinion of a medical examiner is equivalent to that of a treating

physician and should be afforded the same consideration. Nordwall ex rel. Tori v. Sec’y of Health

& Human Servs., 83 Fed. Cl. 477, 488 (2008) (“An autopsy report by a medical examiner is without

question a contemporaneous medical record”). Accordingly, I find that Robert suffered from

lymphocytic, not eosinophilic, myocarditis.

2. Althen Analysis

43

i. Althen Prong One: Petitioner Has Failed to Proffer a Reputable

Medical Theory that the Menactra Vaccine Can Cause Lymphocytic

Myocarditis

Petitioner offered two theories in this case. The first based on a statement found in an article

that “[M]eningococcal conjugate vaccines, through conjugation of polysaccharide to a protein

carrier, change the immune response from T-cell independent to T-cell dependent, leading to

improved immunogenicity over polysaccharide vaccines,” which Dr. Waters stated meant that T-

lymphocytes generated by the immune system in response to the Menactra vaccine “gravitated to

the heart’s conduction system causing a lethal arrhythmia and sudden death.” Pet. Ex. 13 at 6-7,

referencing Pet. Ex. 21 at 1. “The fact that we have a lymphocytic response is certainly very

consistent with the cause being the vaccine and the time course is appropriate.” Tr. 56-57. Dr.

Waters provided no explanation for how the T-cell mediated immune response to the Menactra

vaccine compares with the pathogenesis of lymphocytic myocarditis.

When asked if there was any literature which supported her opinion that Menactra vaccine

could cause lymphocytic myocarditis, Dr. Waters stated that the package insert discussed the

mechanism of action for the vaccine through T-lymphocytes. Tr. 78. “Moreover, the

meningococcal vaccines are relatively new and have not been as widely distributed as smallpox or

DTP which have both demonstrated vaccine-caused myocarditis.” Pet. Ex. 13 at 7. To that end,

Dr. Waters was asked to confirm that Barton, when discussing two cases of eosinophilic

myocarditis following vaccination, had concluded that, if evidence existed for an association

between myocarditis and meningococcal vaccine, it would be eosinophilic, not lymphocytic,

myocarditis. Dr. Waters responded, “It suggests that in two out of their two cases the eosinophilic

part was histologically seen.” Tr. 77-78. Dr. Waters admitted that those were the two cases she

referred to and based her report on.

Dr. Waters’ theory that the meningococcal vaccine can cause lymphocytic myocarditis

was premised on the body’s intended response to the Menactra vaccine through T-cells in order to

create immunity. Dr. Waters could point to nothing in the record to support the theory that this

process or any vaccine including the meningococcal vaccine could cause lymphocytic myocarditis.

Furthermore, Dr. Waters did not and could not provide any literature to support her opinion that

lymphocytic myocarditis has been associated with drugs, toxins, or vaccines. All of the literature

submitted in this matter by both petitioner and respondent unequivocally described lymphocytic

myocarditis as an inflammation due to lymphocytes and macrophages commonly associated with

viral syndrome, and eosinophilic myocarditis as associated with allergic or hypersensitivity

reactions to drugs, toxins, vaccines, parasites, and cancer. Even in cases where mixed infiltrates

were found, the presence of eosinophils was the determining factor in distinguishing lymphocytic

myocarditis from eosinophilic myocarditis. Succinctly, Dr. Waters could not explain how the

Menactra vaccine could cause lymphocytic myocarditis, nor could she point to any literature

showing any association between vaccines and lymphocytic myocarditis.

Petitioner’s second theory was that the Menactra vaccine can cause a hypersensitivity

reaction resulting in lymphocytic myocarditis and cardiac death. Dr. Waters joined Dr. Chang on

this theory. Dr. Waters opined that the Menactra vaccine can cause an anamnestic T-lymphocyte

44

cell response to the Menactra, which causes inflammation leading to a hypersensitivity response.

Dr. Waters suggested that a Type IV hypersensitivity reaction only produces lymphocytes. Tr. 68-

69, 83. However, Dr. Waters admitted that hypersensitivity myocarditis by definition is

eosinophilic. Tr. 65. She hedged, “I think hypersensitivity myocarditis can present histologically

as either lymphocytic myocarditis or eosinophilic myocarditis.” Tr. 66. However, she was unable

to point to any literature in the record that supported this proposition other than to say that Byard

infers it, “but it’s – as I mentioned before, hypersensitivity is more—is a clinical term.” Tr. 66-67.

Dr. Chang maintained that the Menactra vaccine caused a hypersensitivity reaction, stating

that an inflammatory process from vaccination could lead to either eosinophilic and/or

lymphocytic myocarditis. However, when asked about the distinction made between lymphocytic

myocarditis as viral and eosinophilic myocarditis as a hypersensitivity reaction, Dr. Chang

submitted that it did not matter how the myocarditis was classified because clinically, patients do

not always fit all of the criteria for certain classifications. Tr. 204-05. Further, Dr. Chang stated

that the type of myocarditis did not matter to him because it would not change the way that he

would treat the patient. Tr. 197, 218. Dr. Chang’s responses in this case begs the question of why

he was asked to serve as an expert in this case.

Dr. Folkerth testified that there is no pathophysiological support for Dr. Waters’ theory.

Although Menactra, like any other drug or vaccine, could cause an allergic reaction or

hypersensitivity response in a sensitive person, such a response would be characterized by

eosinophils. Tr. 128-31. A hypersensitivity myocarditis could have a mixed infiltrate with

eosinophils and lymphocytes, but not lymphocytes alone. Tr. 99-100; see also Pet. Ex. 17 at 3

(“Clinically, hypersensitivity myocarditis is indistinguishable from myocarditis resulting from

other causes. The nature of the inflammatory infiltrate present in myocardial tissue biopsy is a key

for differentiating

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