More than one hundred cases of reported adverse reactions after HPV vaccination have been excluded from Australia’s public Database of Adverse Event Notifications (DAEN) and are only recorded in the Therapeutic Goods Administration’s private database.

The 101 cases included in the TGA’s Adverse Event Management System (AEMS) internal database that do not appear in the DAEN include deaths, four cases of cervical cancer¹, two cases of ovarian cancer, and reports of pancreatitis, premature menopause, paralysis, and multiple sclerosis.

One case from 2014 (age unspecified) is reported as “cervix neoplasm; vaccination failure”.

In another case, from 2007, (female, age unspecified) the reported adverse reaction is described as “carcinoma in situ”, but no further details are given.

Only one report of cervical cancer is listed in the DAEN. The report was made in 2010 and concerns a 24-year-old woman.

In many of the cases recorded in the internal database, individuals report numerous adverse reactions. Symptom clusters are commonplace worldwide in reports of adverse reactions to HPV vaccination.

In one case in the AEMS database, more than 30 adverse reactions are reported by one 15-year-old girl.

There is one report in the AEMS database of a neonatal death after vaccination with quadrivalent Gardasil. No details are given as to how the baby came to be injected when the recommended starting age for HPV vaccination is nine.

The public DAEN database lists 4,867 adverse reactions reported after HPV vaccination up until February 27 this year, including 233 reporting as relating to Gardasil 9, which was rolled out in Australia in 2018.

A total 4,329 reports are listed as relating to quadrivalent Gardasil, and a further 84 reports relate to what is referred to as “Human Papillomavirus Recombinant Vaccine Quadrivalent”, which is, in fact, Gardasil (one of these is a reported death).

Fifteen reports relate to Cervarix and the remaining reports are listed under the category “Tradename not specified (active ingredients: HPV Type 16 L1 Protein; HPV Type 18 L1 Protein)“. 

The TGA explains that this category is used when a report does not contain sufficient information to determine which HPV vaccine was administered. Reference is made to the two strains common to all HPV vaccines, type 16 and type 18.

The internal AEMS statistics, which relate mainly to quadrivalent Gardasil, have only come to light thanks to a Freedom of Information (FOI) request made by Michelle Stubbs, whose daughter Asha became seriously ill after HPV vaccination.

Stubbs, who lives in northern Queensland, is organising a class action lawsuit against Merck, who manufacture Gardasil and Gardasil 9. For the past couple of years she has been doggedly chasing up information, putting questions to the TGA and the Department of Health about her daughter’s case and HPV vaccination in general.

She was shocked to discover that a nurse or pharmacist can request exclusion from the DAEN of a reported adverse reaction, even in circumstances where a doctor reported the reaction.

“The TGA have confirmed to me in writing that the health professional that makes the call not to publish a reported adverse effect on the DAEN could be a nurse, a pharmacist, or a doctor,” Stubbs told Changing Times.

The TGA stated in an email to Stubbs: “When the TGA receives an adverse event report it is entered into the Adverse Event Management System by staff in the Pharmacovigilance and Special Access Branch.

“If there appears to be insufficient information and/or no reasonable temporal association and/or the relationship between the medicine/vaccine and the adverse event appears to not be related, the cases are reviewed by a health professional (doctor, nurse or pharmacist), who may seek further information from the reporter.”

The TGA told Stubbs that about 90 percent of the reports it receives are included in the DAEN and added that “the vast majority of the reports not included in DAEN are either duplicate reports for a single case or reports for unregistered medicines”.

Stubbs questioned the TGA after she saw the report of a death that she thought had to be that of 16-year-old Gabby Larkin removed from the DAEN.

Larkin, from Mont Albert North in the Australian state of Victoria, died on June 4, 2009, at the age of 16. She had an extremely rare form of ovarian cancer.

Patrice Larkin with a photo of her daughter Gabby.

The DAEN and internal database reports never include names so it is not clear whether the June 2009 report that appears only in the AEMS internal database and concerns a 16-year-old girl developing ovarian cancer refers to Larkin, but it would be very surprising if it was not her case. There is no report currently publicly available that appears to refer to her death.

There are three deaths reported that are only recorded in the AEMS internal database. They include one neonatal death.

On the TGA website, in an update dated May 13, 2015, the TGA states: “There have been no reports of death associated with Gardasil vaccination in Australia.”

However, one of the deaths recorded in the AEMS internal database occurred in 2009 (the neonatal death) and another occurred in 2009.

The one reported death recorded in the DAEN database can only be seen by searching in the category “Human Papillomavirus Recombinant Vaccine Quadrivalent”, not under Gardasil. The death is recorded both in the “Medicine summary” section as “vaccination failure” and “cervix carcinoma”, but there is no detailed report that refers specifically to the death. The TGA told Changing Times that the report relates to a death in March 2016.

The following case appears in the DAEN, in the “List of reports” section,  but it is not reported there as a death. The TGA confirms, however, that there was a “fatal outcome” in this case, so one would deduct that it is the same case as the case of a death referred to above.

In the internal AEMS database, there is a report of an induced abortion after what is described as “exposure” to quadrivalent Gardasil during pregnancy.

Merck itself says that the safety and effectiveness of Gardasil has not been established for pregnant women.

There is one case in the internal database, reported in October 2017, of a 15-year-old girl who reports a staggering list of adverse effects, including abdominal pain, a loss of consciousness, muscular weakness, a cardiac disorder, vomiting, food intolerance, gait disturbance, blurred vision, arthralgia (joint pain) and paraesthesia (an abnormal sensation, typically a tingling or pricking feeling) after vaccination with Gardasil. This case also does not appear in the DAEN.

There’s also an extraordinary case, reported in 2007, in which a woman aged 77 suffered several adverse effects after receiving a cocktail of drugs along with a Cervarix vaccination. (Cervarix is manufactured by GlaxoSmithKline.)

There’s a report from 2009 detailing how a 49-year-old woman suffered throat pain after what is described as “inappropriate schedule of drug administration” (a Gardasil injection).

There are three reports of paraesthesia in the internal data base that have never appeared in the DAEN.

Other cases in the internal database that have never been reported in the DAEN include eight reports of anaphylactic reaction, including three on the same day.

In one case of anaphylactic reaction, a 12-year-old boy had received Boostrix (tetanus, diphtheria and pertussis) and Gardasil 9 vaccinations together. The adverse reaction was on the same day.

There are seven reports of seizures, three reports of paralysis, three reports of Complex Regional Pain Syndrome (CRPS), one case of neonatal sepsis, and two cases of multiple sclerosis (MS) reported after vaccination with quadrivalent Gardasil that are only listed in the internal data base, plus 12 cases of MS that are recorded in the DAEN.

In one case, reported in May 2016, that is listed in the DAEN, a 21-year-old woman is reported as having an MS relapse and optic neuritis (an inflammation that damages the optic nerve) after being injected with quadrivalent Gardasil.

In one of the seizure cases listed only on the internal database, the person, whose age and sex are not available, also reported gait disturbance, hallucination, and pain in extremities.

In one of the cases of paralysis, the multiple reactions reported include a balance disorder, dysphagia (swallowing difficulties), parosmia (a distortion of the sense of smell), and pyrexia (raised body temperature).

There is also one report from 2011, that is only in the internal database, of a case of Guillain-Barré syndrome. The report relates to a female, whose age is not available, who was injected with quadrivalent Gardasil.

In a 2017 public assessment report about Gardasil 9 the TGA includes a response from Merck, which states that the company “has closely monitored events of autoimmune disease reported as temporally associated with the administration of Gardasil as part of regulatory commitments”.

As a part of this routine monitoring processes, the adverse events of Guillain-Barré syndrome (GBS) and acute disseminated encephalomyelitis (ADEM) were spontaneously reported during post-approval use of quadrivalent Gardasil and were added to the company’s vaccine core data sheet (CCDS) in 2007 and 2009 respectively, Merck told the TGA.

Merck added: “Because these experiences were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or to establish a causal relationship to vaccine exposure. The cause of GBS remains unknown, but may involve a nonspecific immune stimulus such as vaccination or infection.

“GBS was added to the CCDS in order to alert health care providers to these reports. The term acute disseminated encephalomyelitis was added to the post-marketing AE section of the CCDS due to the seriousness of the disease.”

The TGA, however, has decided that at least one case of Guillain-Barré syndrome should be excluded from the database that is available to the public.

There are four reports of GBS in the DAEN relating to quadrivalent Gardasil. (In two of the cases Gardasil was given on its own.)

Four cases of ADEM are listed in the DAEN in relation to quadrivalent Gardasil. (In two of the cases Gardasil was given on its own.)

There are two cases of meningitis listed only in the TGA’s internal database, along with one case of a blood disorder, and two reports of pancreatitis, one of which concerns a 13-year-old girl. (The age in the second case is unavailable.) There is one report, from 2011, of a 16-year-old girl having Still’s disease, which is a rare systemic autoinflammatory condition.

The TGA insists that there is no link between HPV vaccination and pancreatitis. A spokeswoman told Changing Times in an email that, following several reports of pancreatitis in 2007 and 2008, the TGA conducted an investigation that concluded that a causal association between Gardasil and pancreatitis could not be established.

There have, however, been numerous cases of people in a number of countries developing chronic pancreatitis after HPV vaccination. One case of chronic pancreatitis after a Gardasil vaccination in 2009 is listed in the DAEN.

A group of doctors in Australia have drawn a link between HPV vaccination and the pancreatitis suffered by a young woman after she was vaccinated with quadrivalent Gardasil.

In a letter to the editor of the Medical Journal of Australia, published in August 2008, surgeons Amitabha Das and Neil Merrett, surgeon and researcher David Chang, and head of the Sydney-based Pancreatic Cancer Research Group, Andrew Biankin, said an extensive investigation of the case could find no other cause for the pancreatitis.

They said that, while a coincidental illness causing pancreatitis could not be ruled out, “neither can HPV vaccination be excluded as a potential cause”.

They added that “the close temporal relation of the HPV vaccination, the development of a prodromal² illness, and fever without evidence of sepsis led us to postulate that pancreatitis was secondary to vaccination”.

They suggested that pancreatitis be considered in cases of abdominal pain following HPV vaccination and, if proven, be notified to the Adverse Drug Reactions Advisory Committee.

The DAEN contains ten reports of pancreatitis following Gardasil vaccination and in nine of those cases Gardasil was administered on its own.

Other reports that appear only in the AEMS internal database include one case of premature menopause, one of brain injury, one of hypertrophic cardiomyopathy³ (the patient died), and one of leukaemic infiltration (that occurred with along with facial paralysis), four cases of lymphadenopathy⁴, one case of nephritis (kidney inflammation), one case of polyneuropathy (damage or disease affecting peripheral nerves), and three cases of oropharyngeal pain (pain in the throat). Numerous other cases of lymphadenopathy are reported in the DAEN.

There are also numerous cases of fainting, rashes, coughs, and general malaise that are listed only on the internal database.

In the case of the report about brain injury, it is stated that the person in question, whose age and sex are not available, received both Cervarix and Gardasil shots. Only two other reports in the internal database relate to Cervarix.

There are also three reports of disease progression that appear only in the internal database. In one case the female patient has a motor neurone disorder. In another case, a 12-year-old boy is reported to have suffered from concomitant disease progression and seizure two weeks after receiving Boostrix and Gardasil injections at the same time. The disease he was suffering from is not specified.

In another report that concerns a vaccinated boy the adverse reaction is described as “disability”, with no further clarification.

There are four reports of what is described as “vaccination failure”. In one case the report refers to “Cervix carcinoma; vaccination failure”, another refers to cervix neoplasm, and one refers to anogenital warts. There are also “vaccination failure” reports on the DAEN.

In response to her FOI request Stubbs was sent a list of other reports that were previously published in the DAEN, but were being updated.

The TGA explained that a new internal database was introduced in mid-2018, and data was transferred from the old to the new database.

“While all reports were migrated, some reports had insufficient information coded for the medicine/vaccine name. These reports are currently being reviewed and manually updated to enter the coded medicine/vaccine name, which is required for the report to be published on the DAEN,” the TGA stated.

Of the 227 reports listed, 205 had previously been published in the DAEN, and would be available in the DAEN in the future once the vaccine name had been updated, the TGA added.

“There are 22 reports that will not be published on the DAEN as they either have insufficient information and/or no reasonable temporal association and/or the relationship between the medicine/vaccine and the adverse event appears to not be related as judged by a health professional and/or the report may be a duplicate of a report included in the DAEN,” the TGA stated.

The 18 reports that are duplicates are highlighted in the table provided.

Information provided on the TGA website.

DAEN reports

There is just one reported case of cervical cancer occurring after vaccination with quadrivalent Gardasil listed in the DAEN.

Also in relation to quadrivalent Gardasil, there are 82 reported cases of seizures and 128 reports of myalgia (muscle pain). Twenty cases of tachycardia are listed along with seven cases of postural orthostatic tachycardia syndrome (POTS), two cases of an unspecified malignant neoplasm, and one case of arrhythmia (a group of conditions in which the heartbeat is too fast, too slow, or irregular). There are two reported cases of Still’s disease.

There are ten reported cases of hallucination, seven of premature menopause, and five cases of exposure during pregnancy. One case is recorded of premature labour, one of acute kidney injury, and one of ovarian failure.

There are thirty cases in the DAEN of anaphylactic reaction after vaccination with Gardasil (24 of which are cases in which Gardasil was given on its own) and one case is reported after vaccination with Gardasil 9.

The database also contains thirty reports of photophobia (extreme sensitivity to light), and two cases in which the adverse reaction is reported as a malignant neoplasm ( a cancerous tumour).

There are also three reports of spontaneous abortion in cases in which Gardasil is given on its own.

Reports on the DAEN of adverse reactions after vaccination with quadrivalent Gardasil, up to February 24, 2019.

Gardasil 9

In the case of Gardasil 9, up to February 25, 2019, DAEN lists 27 cases of pyrexia, 19 cases of pain in extremities, 17 cases of vomiting, and 14 cases of general malaise.

The most common adverse effects, after injection site reactions, are fainting, headaches, rashes, and nausea. There is one reported case of ovarian failure after vaccination with Gardasil 9, one report of Guillain-Barré syndrome, one of hallucination, one of hemiparesis (muscular weakness or partial paralysis restricted to one side of the body), and one of a malignant neoplasm.

There is one report of infertility after vaccination with Gardasil 9, one report of a psychogenic seizure, and one of demyelination. A demyelinating disease is any condition that results in damage to the protective myelin sheath that surrounds nerve fibres in the brain, optic nerves, and spinal cord. When the myelin sheath is damaged, nerve impulses slow or even stop, causing neurological problems.

There are reports from individuals aged 27, 32, 33, and 43, mostly from 2019.

The Food and Drug Administration in the United States only expanded Gardasil 9’s approved use to include women and men aged 27 to 45 in October 2018 and Merck states that quadrivalent Gardasil is indicated for ages nine to 26.

However, in Australia, quadrivalent Gardasil was registered to be given to females aged 9–45 years and males aged 9–26 years in 2006. The bivalent vaccine Cervarix was registered to be given to girls and women aged 10–45 years in 2007. Gardasil 9 was registered to be given to females aged 9–45 years and males aged 9–26 years in June 2015.

The TGA under scrutiny, and under fire

The report to the TGA of Asha Stubbs’ case does appear in the DAEN, but there were mistakes made that her mother says she had to correct. Asha’s age was incorrect and her second myelodysplastic syndrome (MDS) diagnosis was left out. The date of the first MDS diagnosis was also incorrect.

During the FOI process, Stubbs applied to have her costs waived because of financial hardship and because she believed the information she requested was in the public interest.

The TGA decision maker said he was not satisfied that payment of the $128.40 fee would leave Stubbs unable to provide food, accommodation, clothing, medical treatment, education, or other necessities for herself or her family, or other people for whom she might be responsible.

He said he was therefore not satisfied that paying the $128.40 would cause Stubbs “financial hardship” within the meaning of the FOI guidelines.

He said, however, that he had decided to exercise his discretion to reduce the fee by 50 percent on the basis that Stubbs was in receipt of a Centrelink carer allowance and carer payment which, he said, appeared to indicate that her income was limited.

The TGA decision maker also said he did not believe that the information requested by, and provided to, Stubbs was of interest to the general public.

“I was furious about this,” Stubbs said. “Paying for this FOI request took food from my sick daughter’s mouth.

“I could have appealed against this decision, but I was too angry to. I did send the decision maker an honest and frank response about how his decision made me feel.

“More than one hundred cases of adverse reactions excluded from the public database. Of course that is in the public interest.”

There is criticism of the fact that the TGA both approves drugs and vaccinations and also monitors their safety.

“There is a clear conflict of interest there,” Stubbs said. “It’s time that the reporting of adverse reactions to drugs and vaccinations was mandatory. There should be a reliable system in place that does capture all relevant information. Then, we would not lose so many reports because of a lack of information.”

The TGA was heavily criticised in the 2010 Stokes review, which analysed the public health response to adverse reactions to the seasonal influenza vaccine that were experienced by children in Western Australia.

The 2010 seasonal influenza vaccination programme was stopped about four weeks after it began because of an alarming rise in adverse events following vaccination.

Stokes’ review, which was ordered by the Western Australian minister for health, revealed what appeared to be a serious deficiency in the mechanisms for reporting these adverse events.

Stakeholders and independent specialists who were consulted during the review process raised concerns about perceived conflicts of interest. (Expert members of bodies responsible for monitoring vaccination are also involved in pharmaceutical companies and clinical trials for vaccines.)

One of Stokes’ recommendations was that the Commonwealth Department of Health and Ageing (DoHA) formally review and address any perceived or real concerns about conflict of interest in these “peak bodies”.

Stokes concluded that Australia’s National Immunisation Committee (NIC), which is the “peak body” for the country’s National Immunisation Programme, had made little progress in implementing recommendations from a National Vaccine Safety Workshop in 2006 that were aimed at improving national surveillance of adverse effects following vaccination.

He added: “It is disturbing that neither this State nor the Commonwealth put in place the measures recommended by the World Health Organisation (WHO) in August 2009 regarding the surveillance and reporting of adverse events following the introduction of pandemic vaccination programmes.”

The WHO recommendations were put in place when Australia conducted the H1N1 vaccination programme in 2009, Stokes pointed out.

“It is unfortunate in the reviewer’s mind that these recommendations have not been continued in the routine vaccination programmes in this country and especially in Western Australia when in the 2010 vaccination program against seasonal influenza, a vaccine significantly different from previous years was being used, and when the programme involved young children from six months to five years,” he said.

Stokes said the dual mechanism of reporting adverse events to either the TGA branch of the DoHA or to the public health division of the state Department of Health (DoH) was confusing and did not allow for a timely and comprehensive collection of data on these events.

“This combined with the lack of knowledge at any given time of the number of vaccinations already given so that the rate of adverse events could be quickly calculated added further to reporting difficulties.”

Stokes said his review had revealed an adverse event reporting system that was not robust or timely and did not conform to WHO recommendations concerning mass immunisation programmes.

One of the recommendations of the Senate Community Affairs References Committee Inquiry about transvaginal mesh implants was that the Australian government, in consultation with the states and territories and the Medical Board of Australia, review the current system of reporting adverse events to the TGA.

In its report, which was published in March 2008, the committee recommended that the government implement mandatory reporting of adverse events by medical practitioners, provide guidance on what constitutes an adverse event for use by consumers, medical practitioners and device sponsors, improve awareness of the reporting system, and examine options to simplify the reporting process.

The committee noted the “vital role of adverse reporting in post-market surveillance”.

It’s clear that any analysis of many of the reports submitted about adverse reactions to HPV vaccination would be made more difficult by the fact that the HPV vaccines are often administered at the same time as another vaccine, for example the Hepatitis B and/or the DTPa vaccine.

The figures 0 and 1 refer to onset times. (0 = an adverse reaction the same day as vaccination and 1= the next day).

While members of the public cannot access the AEMS system, “sponsors” can access it by using their TGA “business services” account.

Michelle Stubbs says no adverse reaction reports should be hidden from the public.

“I find the entire way the TGA manages adverse reaction reports to vaccines to be indicative of its role of being the regulator who deemed the vaccines safe for market,” she said.

“To adequately manage post-market safety data, the TGA would effectively be proving themselves wrong. We are potentially talking about thousands of vaccine-injured children who are literally being ignored.”

Stubbs says that, despite the fact that her daughter received an autoimmune blood disorder diagnosis two weeks after Gardasil “stimulated” her immune system and has suffered 11 years of serious illness with a poor prognosis, the TGA has never investigated what happened to Asha.

“I had to lodge a formal complaint before they would even tell me that they hadn’t carried out any investigation into her case.”

Asha’s life has been destroyed, Stubbs says. “Vaccine-injured children in Australia deserve acknowledgement and assistance. Reports of adverse reactions to vaccines should be mandated and those reports need to be managed properly and include enough information to facilitate an investigation.

“It’s not good enough that the TGA appears to just sit back and watch the data grow. These reports primarily relate to children and many of them are about significant health issues.”

Michelle and Asha.

Asha Stubbs, who is originally from Albany, Western Australia, but lives in northern Queensland, received her first two Gardasil injections in July 2007 and October 2007 when she was 15 years old. When she received her third injection in March 2008, she was 16.

Two weeks after that injection, Asha was diagnosed with idiopathic thrombocytopenic purpura (ITP), a rare autoimmune disorder in which a person’s blood doesn’t clot properly because the immune system destroys the blood-clotting platelets.

When Asha was 19, the ITP turned into paroxysmal nocturnal hemoglobinuria (PNH), which is a rare and life-threatening blood disease in which red blood cells are destroyed and blood clots develop.

About six months later Asha was also diagnosed with myelodysplastic syndrome (MDS), in which the bone marrow does not produce sufficient healthy blood cells. She was told she was in the early stages of developing acute myeloid leukaemia (AML).

There is more detail about Asha’s case in this Changing Times article.

1) One additional case of cervical cancer recorded in the material obtained by Michelle Stubbs is listed in the second section of the document. It is not clear whether it was previously recorded in the DAEN and whether it will be listed there in the future. The other four cases are recorded in Table 1: “Cases in Adverse Event Management System that do not appear on the DAEN, and are not duplicate reports of cases in the DAEN.”

2) A prodrome is an early sign or symptom (or set of signs and symptoms), which often indicate the onset of a disease before more diagnostically specific signs and symptoms develop.

3) Hypertrophic cardiomyopathy is a condition in which a portion of the heart becomes thickened without an obvious cause. This results is the heart being less able to pump blood effectively.

4) Lymphadenopathy, or adenopathy, is disease of the lymph nodes, in which they are abnormal in size or consistency. 

According to the World Health Organisation’s pharmacovigilance database VigiBase, there have been 91,863 reports of adverse reactions following HPV vaccination worldwide.

Details of Michelle Stubbs’ FOI request and the pdf of the information she received will be published on the TGA website next week. (Stubbs’ name will not be given, but all the data she obtained will be shared.)

UPDATE: The documents released to Michelle Stubbs are now available here.

Update 07/06/2019:

The TGA says that the following case “was not considered to be related to the vaccine based on clinical review and consideration of the information provided by the reporter”. It is therefore not included in the DAEN.

The TGA confirms that there was a fatal outcome in case 377263, which was reported in March 2016, and is listed in the DAEN. While this death is referred to, without a detailed report attached, under the “Medicine summary” tab, the entry under the “List of reports” does not refer to a death.

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