Open Access

Post-vaccination myositis and myocarditis in a previously healthy male

  • Matthew P. Cheng1Email author,
  • Michael G. Kozoriz2,
  • Amir A. Ahmadi3,
  • John Kelsall4, 5,
  • Katryn Paquette6 and
  • Jake M. Onrot5
Allergy, Asthma & Clinical Immunology201612:6

https://doi.org/10.1186/s13223-016-0114-4

Received: 25 September 2015

Accepted: 17 January 2016

Published: 11 February 2016

Abstract

Background

The immunological literature has been redefining clinical phenomena as hypotheses emerge regarding causal links between triggers, immunologic manifestations, and their specific inflammatory cascades. Of late, autoimmune manifestations that appear to be caused by an external adjuvant have been grouped into a complex syndrome referred to as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This syndrome may present with diverse clinical problems, which may include neurocognitive impairment, inflammatory musculoskeletal changes, and constitutional symptoms. There is evidence in the literature linking vaccines to different auto-immune manifestations. Vaccines have not traditionally been reported to trigger ASIA, although reports are emerging linking the human papilloma virus and hepatitis B vaccines to it.

Case presentation

We report the first suspected case of ASIA in a previously healthy patient who received the Fluad seasonal influenza vaccine, which contains the MF59 adjuvant. He presented to hospital with profound weakness and was diagnosed with severe rhabdomyolysis. He also had elevated troponin-I and extensive cardiac investigations enabled the diagnosis of myocarditis. His infectious and rheumatologic work-ups were negative. He responded well to conservative management and did not require immune suppressive therapy.

Conclusion

Given the benefits of the influenza vaccine, and the low incidence of clinically significant complications, we encourage ongoing seasonal influenza immunization. However, ongoing surveillance is required to evaluate the occurrence of rare adverse events, including ASIA.

Keywords

Vaccine Myocarditis Rhabdomyolysis Autoimmune ASIA

Background

Adjuvants are elements that induce an inflammatory response. In the case of vaccines, adjuvants increase the antigen-specific immune response, to ultimately improve vaccine immunogenicity. This process may also have negative repercussions, inducing autoimmunity. Since 2011, autoimmune manifestations that appear to be caused by an external adjuvant have been grouped into a complex entity referred to as autoimmune/inflammatory syndrome induced by adjuvants (ASIA) [1, 2]. Previously referred to as Shoenfeld’s syndrome, the disorder has been redefined; it is characterized by neurocognitive, inflammatory musculoskeletal, and/or constitutional symptoms upon exposure to an external stimulus, improvement following withdrawal of the offending agent, and may involve the development of autoantibodies, specific HLA phenotypes or evolution into a rheumatological disorder [3]. The exact mechanisms linking external adjuvants to the various immune responses described are not known.

There is longstanding literature linking vaccines to different auto-immune manifestations [4]. In recent years, immunizations [57], especially the human papilloma virus and hepatitis B virus vaccines [8], and various vaccine adjuvants [9, 10] have been linked to ASIA. However, the seasonal influenza vaccine is an uncommon trigger for autoimmune disease, and is not commonly associated with rhabdomyolysis or myocarditis. One study showed a tendency for autoantibody production in adults following the influenza vaccine, but without clinical disease correlation [11]. We report the first suspected case of a seasonal influenza vaccine induced-ASIA in a previously healthy male who presented to hospital with simultaneous rhabdomyolysis and myocarditis.

Case presentation

A 65 year old previously healthy male presented to hospital with profound weakness. Five days before admission, he had received the Fluad seasonal influenza vaccine, comprised of one influenza A H1/N1 virus, one influenza A H3/N2 virus, one influenza B virus, and the MF59 adjuvant. Two days later, he developed bilateral crampy leg pain, muscle tenderness, and progressive weakness. He became unable to weight-bear and was brought to the emergency department by his wife. He denied experiencing headaches, paresthesias, arthralgias, skin lesions or constitutional symptoms. An infectious review of systems was unremarkable. He was not taking any medications or herbal preparations prior to admission, nor did he use recreational drugs.

On physical exam his vital signs were: pulse 92/minute, blood pressure 124/84, respiratory rate 20/minute, oral temperature 36.7 °C, and his oxygen saturation was 100 % on room air. His neurological exam was significant for 4/5 strength in bilateral hip flexors, hip extensors, hip abductors and hip adductors. He could not stand from the sitting position without the aid of his arms. The large muscle groups of his arms and legs were tender. Cardiac examination revealed a jugular venous pressure (JVP) two cm above the sternal angle, a normal apical beat, a normal S1 and S2 without any extra heart sounds, murmurs or rubs. His respiratory exam revealed mild crackles in the left lower lobe. The remainder of the examination was unremarkable.

His blood counts were WBC 11 × 99/L, hemoglobin 123 g/L (MCV 83 fL) and platelets 134 × 109/L. Electrolytes included sodium 126 mmol/L, potassium 3.2 mmol/L, chloride 101 mmol/L, bicarbonate 17 mmol/L, phosphate 0.75 mmol/L and magnesium 0.97 mmol/L. Other laboratory parameters included urea 11.6 mM/L, creatinine 157 mM/L, creatine kinase (CK) 7736 U/L (normal < 150 U/L) and troponin-I 9.44 mcg/L (normal < 0.2 mcg/L). A blood ethanol level was negative. His EKG revealed normal sinus rhythm and a right bundle branch block, without ischemic features. A chest radiograph and contrast enhanced computed tomography scan of the chest revealed a hiatus hernia, left lower lobe opacification, without evidence of pulmonary embolism.

Acute rhabdomyolysis was diagnosed and the patient received four liters of fluid over the ensuing 24 h. During volume resuscitation, he developed pulmonary crackles, his JVP increased to 5 cm above the sternal angle, and his oxygen saturation decreased to 90 % on room air. Supplemental oxygen and a single dose of furosemide 40 mg IV were provided, to which he responded well. He also initially received piperacillin–tazobactam for possible left lower lobe pneumonia. No steroids were prescribed. His creatinine, CK and troponin levels trended downwards after 12 h of therapy, and almost normalized within 5 days (see Fig. 1).
Fig. 1

Trend of patient's creatine kinase and troponin-I

A basic immunological workup was within normal limits, with an antinuclear antibody test (ANA) of 1:160, homogeneous pattern (non-specific), and negative anti-dsDNA, ENA panel, C3, C4, rheumatoid factor, and ANCA tests. Serum protein electrophoresis (SPEP) was consistent with an acute phase reaction and urine protein electrophoresis (UPEP) was negative. Dipstick urinalysis revealed 1+ protein and 1+ blood and his urine was positive for myoglobin. Microscopy revealed granular casts, urate crystals and no evidence of red blood cells. HIV, hepatitis B and C serological tests were negative. Blood and urine cultures yielded no growth. Computed tomography scans of the head and lumbar spine were negative; no other cause was found to explain the patient’s weakness. An echocardiogram performed on day three of admission revealed normal biventricular systolic function without regional wall motion abnormalities. Cardiac MRI on day four confirmed the diagnosis of myocarditis. A muscle biopsy was not performed as the patient recovered promptly; he was discharged home on day six.

Discussion

This patient presented with a gradual onset of weakness and muscular pain. He had received the influenza vaccine 5 days prior to the onset of symptoms. Laboratory investigations indicated rhabdomyolysis, myocarditis, and acute kidney injury, which all resolved by the sixth day of admission.

In rhabdomyolysis, there is breakdown of skeletal muscle cells, resulting in the release of cellular constituents such as electrolytes, myoglobin and cellular enzymes, including creatine kinase. The consequences thereof can include life threatening disseminated intravascular coagulation, electrolyte disturbances, and acute kidney injury. There are numerous known causes of rhabdomyolysis [12, 13]; they are summarized in Table 1.
Table 1

Common causes of rhabdomyolysis

Category

Example

Autoimmune diseases

Dermatomyositis and polymyositis

Drugs and toxins

Numerous: including alcohol, cocaine, heroin, fibrates and statins

Electrolyte disorders

Hypokalemia, hypernatremia, hyponatremia, hypophosphatemia, hypocalcemia, hyperosmolarity, ketoacidosis

Endocrine disorders

Hypothyroidism, hyperaldosteronism

Excessive muscle activity

Alcohol withdrawal, exercise, seizures

Genetic disorders

Numerous: including disorders of glycolysis, glycogenolysis, lipid metabolism, mitochondrial pathways and nucleotide metabolism

Hypoxia

Prolonged immobilization, artery occlusion

Idiopathic

 Infections

Viral (coxsackievirus, Epstein–Barr virus, herpes viruses, HIV, influenza A and B)

Bacterial (Clostridium spp., F. tularensis, L. pneumophilia, Salmonella spp., S. pyogenes, S. aureus)

Parasitic (malaria)

 Temperature

Heatstroke, malignant hyperthermia, malignant neuroleptic syndrome, hypothermia

 Trauma and compression

Crush injury syndrome, electrical injury

Aggressive fluid management is key in avoiding myoglobin-induced oxidative damage to the kidney [13]. This patient was treated with modest fluid resuscitation, due to the concern of circulatory overload in the context of suspected cardiac myositis. He did indeed develop signs of volume overload (increased JVP and respiratory crackles), with favorable response to decreased fluid administration and a diuretic. In addition to the nephrotoxic effects of myoglobin, recent evidence suggests that pro-inflammatory cytokines, chemokines and NLRP3 inflammasomes partake in the pathogenesis of rhabdomyolysis-induced acute kidney injury [14], highlighting the importance for additional research in the management of this condition.

As the history, physical examination, and laboratory markers did not suggest an alternative cause for rhabdomyolysis, we believe that his presentation was most in keeping with ASIA. Furthermore, he fulfilled many of the major suggested criteria for the diagnosis of ASIA (see Table 2). Connective tissue causes of myositis were ruled out by the normal ANA titer, and negative ENA, C3, C4, RA, and ANCA panels. Illness resolution without anti-inflammatory or immunomodulatory medication also goes against connective tissue diseases. The physical examination, SPEP, UPEP, and CT scans were not suggestive of Guillain–Barré syndrome. His cardiac evaluation suggested myocarditis and not myocardial infarction as a cause for the troponinemia. Unfortunately, while the patient’s blood cultures were negative, the patient did not produce any sputum for culture, and a respiratory polymerase chain reaction (PCR) panel to detect common respiratory pathogens was not obtained. Although infectious etiologies of rhabdomyolosis have been previously well described [1518], we suspect these to be less likely, as the patient denied upper and lower respiratory tract infection symptoms.
Table 2

Criteria suggested ASIA diagnosis

 

Exposure to an external stimuli (Infection, vaccine, silicone, adjuvant) prior to clinical manifestations

Major criteria

The appearance of ’typical’ clinical manifestations:

   Myalgia, Myositis or muscle weakness

  Arthralgia and/or arthritis

   Chronic fatigue, un-refreshing sleep or sleep disturbances

  Neurological manifestations (especially associated with demyelination)

  Cognitive impairment, memory loss

  Pyrexia, dry mouth

Removal of inciting agent induces improvement

Typical biopsy of involved organs

Minor criteria

The appearance of autoantibodies or antibodies directed at the suspected adjuvant

Other clinical manifestations (i.e. irritable bowel syn.)

Specific HLA (i.e. HLA DRB1, HLA DQB1)

Evolvement of an autoimmune disease (i.e. MS, SSc)

For the diagnosis of ASIA, the presence of at least 2 major or 1 major and 2 minor criteria must be apparent. Table reprinted from Journal of Autoimmunity, vol. 36(1), Yehuda Shoenfelda and Nancy Agmon-Levin, ‘ASIA’—Autoimmune/inflammatory syndrome induced by adjuvants, pages 4–8, Copyright 2011, with permission from Elsevier

Few reports propose an association between the influenza vaccine and rhabdomyolysis and/or myocarditis. There are three case reports of rhabdomyolysis following influenza immunization. However, unlike our case, all three patients were taking a statin drug, and none had features of myocarditis. The first two reports describe patients on statin therapy who developed myalgia and progressive weakness within 24 h of receiving the flu vaccine, who were diagnosed with rhabdomyolysis and acute kidney injury [19, 20]. The third published case of rhabdomyolysis was described 1 week post influenza vaccination in a 57 year old renal transplant patient on simvastatin and cyclosporin A [21]. A final case was reported in the literature: a 60 year old gentleman who developed polyarthropathy, orbital myositis and posterior scleritis 10 days after receiving the 1993 Fluvirin vaccine [22]. Given the ocular involvement, he received oral prednisolone and acetazolamide, with dramatic improvement over the next four months.

Shoenfeld et al. [23] suggest grouping different autoimmune manifestations that are seemingly triggered by an external adjuvant into a syndrome complex, referred to as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Numerous mechanisms have been proposed to explain the interaction between adjuvants, immunogenicity, and autoimmunity. Many researchers postulate that individuals who develop autoimmune phenomena following vaccination have a genetic risk or an underlying disease that activates inappropriate immune responses [1, 7, 24, 25]. ASIA is characterized by a myriad of neurocognitive manifestations, including chronic fatigue, cognitive impairment and amnesia, as well as the development of inflammatory musculoskeletal findings including arthritis and myositis [3]. Our patient’s presentation would be more in keeping with the latter end of the disease spectrum. He fulfills the original diagnostic requirements proposed by Shoenfeld et al. (see Table 2) [23]. Although inflammatory myopathies have been well described following vaccination [25], including macrophagic myofaciitis (MMF) [26], the occurrence of myocarditis has not. Furthermore, our patient did not manifest a locally stereotyped or immunologically active lesion at the site of inoculation, which would argue against MMF. Despite the atypical nature of our patient’s presentation, including cardiac involvement, we believe that his profound inflammatory response may be attributed to the recent vaccine in the absence of other causes, especially given the timing of adjuvant exposure.

As described in a recent systematic literature review and meta-analysis, while local injection site pain and headache are known reactions, serious adverse effects following influenza immunization are rare [27]. Though cases of myositis have been described in adults after hepatitis B or BCG vaccination [28, 29], cases linking the influenza vaccine to myositis without confounding factors are rare. Although an argument can be made regarding the patient’s radiographic opacification as a possible confounder, we are not convinced that the patient had an infectious process. Based on the patient’s clinical and laboratory findings, a presumptive diagnosis of ASIA was made.

As mentioned, there is convincing data in the literature that the influenza vaccine is safe and effective (27). Significant complications are rare. In addition to hand-hygiene and respiratory etiquette, immunization is an effective tool to curb the spread of the influenza virus [30]. Annual vaccination has been shown to protect individuals of all ages from the flu, decreasing rates of emergency room visits, hospitalization, and death [31]. These benefits outweigh the mild adverse effects, prompting many countries to continue wide-reaching annual influenza vaccination campaigns [32].

Conclusion

We report the case of a 65-year-old previously healthy male who presented to hospital with acute rhabdomyolysis and myocarditis 5 days after the administration of a seasonal influenza vaccine. This may have been due to the adjuvant in the vaccine, although alternate etiologies cannot be eliminated. At this time, the incidence of rhabdomyolysis and myocarditis post vaccination is limited to case reports. ASIA is an emerging clinical entity, with its share of case reports hypothesizing a causal link with vaccines. Given the benefits of the influenza vaccine, especially in the health care setting and in many vulnerable populations, compared to the rarity of this and other putative complications, we encourage ongoing seasonal influenza immunization campaigns. Furthermore, most available seasonal flu vaccines do not contain any adjuvants. Ongoing surveillance to establish the existence of this posited entity and to evaluate its risks should be pursued.

Consent

Written informed consent was obtained from the patient for publication of this case report.

Declarations

Authors’ contributuions

All of the authors contributed to the conception and design of the article, collected and interpreted the data, drafted the article and revised it for important intellectual content. All authors read and approved the final manuscript.

Acknowledgements

We thank Dr. Caroline Quach (Montreal, Canada) for critical review and insight on earlier versions of this manuscript.

Competing interests

The authors declare that they have no competing interests.

Funding

This study was conducted as part of our routine work.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Division of Infectious Diseases and Department of Medical Microbiology, Glen site, McGill University Health Centre
(2)
Department of Radiology, University of British Columbia
(3)
Department of Cardiology, University of British Columbia
(4)
Division of Rheumatology, University of British Columbia
(5)
Division of Internal Medicine, University of British Columbia
(6)
Department of Pediatrics, University of British Columbia

References

  1. Perricone C, Colafrancesco S, Mazor RD, Soriano A, Agmon-Levin N, Shoenfeld Y. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: unveiling the pathogenic, clinical and diagnostic aspects. J Autoimmun. 2013;47:1–16. doi:10.1016/j.jaut.2013.10.004.View ArticlePubMedGoogle Scholar
  2. Shoenfeld Y, Agmon-Levin N. ‘ASIA’–autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011;36(1):4–8. doi:10.1016/j.jaut.2010.07.003.View ArticlePubMedGoogle Scholar
  3. Carvalho JF, Barros SM, Branco JC, Fonseca JE. Asia or Shoenfeld’s syndrome: highlighting different perspectives for diffuse chronic pain. Acta Reumatol Port. 2011;36(1):10–2.PubMedGoogle Scholar
  4. Cohen AD, Shoenfeld Y. Vaccine-induced autoimmunity. J Autoimmun. 1996;9(6):699–703. doi:10.1006/jaut.1996.0091.View ArticlePubMedGoogle Scholar
  5. Colafrancesco S, Perricone C, Tomljenovic L, Shoenfeld Y. Human papilloma virus vaccine and primary ovarian failure: another facet of the autoimmune/inflammatory syndrome induced by adjuvants. Am J Reprod Immunol. 2013;70(4):309–16. doi:10.1111/aji.12151.View ArticlePubMedGoogle Scholar
  6. Pellegrino P, Perrone V, Pozzi M, Carnovale C, Perrotta C, Clementi E, et al. The epidemiological profile of ASIA syndrome after HPV vaccination: an evaluation based on the Vaccine Adverse Event Reporting Systems. Immunol Res. 2015;61(1–2):90–6. doi:10.1007/s12026-014-8567-3.View ArticlePubMedGoogle Scholar
  7. Soriano A, Nesher G, Shoenfeld Y. Predicting post-vaccination autoimmunity: who might be at risk? Pharmacol Res. 2015;92:18–22. doi:10.1016/j.phrs.2014.08.002.View ArticlePubMedGoogle Scholar
  8. Perricone C, Shoenfeld Y. Hepatitis B vaccination and undifferentiated connective tissue disease: another brick in the wall of the autoimmune/inflammatory syndrome induced by adjuvants (Asia). J Clin Rheumatol. 2013;19(5):231–3. doi:10.1097/RHU.0b013e31829d56f1.View ArticlePubMedGoogle Scholar
  9. Guimaraes LE, Baker B, Perricone C, Shoenfeld Y. Vaccines, adjuvants and autoimmunity. Pharmacol Res. 2015;100:190–209. doi:10.1016/j.phrs.2015.08.003.View ArticlePubMedGoogle Scholar
  10. Pellegrino P, Clementi E, Radice S. On vaccine’s adjuvants and autoimmunity: current evidence and future perspectives. Autoimmun Rev. 2015;14(10):880–8. doi:10.1016/j.autrev.2015.05.014.View ArticlePubMedGoogle Scholar
  11. Perdan-Pirkmajer K, Thallinger GG, Snoj N, Cucnik S, Zigon P, Kveder T, et al. Autoimmune response following influenza vaccination in patients with autoimmune inflammatory rheumatic disease. Lupus. 2012;21(2):175–83. doi:10.1177/0961203311429817.View ArticlePubMedGoogle Scholar
  12. Huerta-Alardin AL, Varon J, Marik PE. Bench-to-bedside review: rhabdomyolysis—an overview for clinicians. Crit Care. 2005;9(2):158–69. doi:10.1186/cc2978cc2978.PubMed CentralView ArticlePubMedGoogle Scholar
  13. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009;361(1):62–72. doi:10.1056/NEJMra0801327.View ArticlePubMedGoogle Scholar
  14. Komada T, Usui F, Kawashima A, Kimura H, Karasawa T, Inoue Y, et al. Role of NLRP3 inflammasomes for rhabdomyolysis-induced acute kidney injury. Sci Rep. 2015;5:10901. doi:10.1038/srep10901.PubMed CentralView ArticlePubMedGoogle Scholar
  15. Blanco JR, Zabalza M, Salcedo J, Echeverria L, Garcia A, Vallejo M. Rhabdomyolysis of infectious and noninfectious causes. South Med J. 2002;95(5):542–4.View ArticlePubMedGoogle Scholar
  16. O’Connor JV, Iyer SK. Myoglobinuria associated with parainfluenza type 2 infection. NY State J Med. 1982;82(10):1469–70.Google Scholar
  17. Pesik NT, Otten EJ. Severe rhabdomyolysis following a viral illness: a case report and review of the literature. J Emerg Med. 1996;14(4):425–8.View ArticlePubMedGoogle Scholar
  18. Ueda K, Robbins DA, Iitaka K, Linnemann CC Jr. Fatal rhabdomyolysis associated with parainfluenza type 3 infection. Hiroshima J Med Sci. 1978;27(2):99–103.PubMedGoogle Scholar
  19. Sun V, Otis-Green S, Morgan R, Wakabayashi M, Hakim A, Callado ME, et al. Toxicities, complications, and clinical encounters during intraperitoneal chemotherapy in 17 women with ovarian cancer. Eur J Oncol Nurs. 2013;17(3):375–80. doi:10.1016/j.ejon.2012.10.005.View ArticlePubMedGoogle Scholar
  20. Plotkin E, Bernheim J, Ben-Chetrit S, Mor A, Korzets Z. Influenza vaccine–a possible trigger of rhabdomyolysis induced acute renal failure due to the combined use of cerivastatin and bezafibrate. Nephrol Dial Transplant. 2000;15(5):740–1.View ArticlePubMedGoogle Scholar
  21. Raman KS, Chandrasekar T, Reeve RS, Roberts ME, Kalra PA. Influenza vaccine-induced rhabdomyolysis leading to acute renal transplant dysfunction. Nephrol Dial Transplant. 2006;21(2):530–1. doi:10.1093/ndt/gfi195.View ArticlePubMedGoogle Scholar
  22. Thurairajan G, Hope-Ross MW, Situnayake RD, Murray PI. Polyarthropathy, orbital myositis and posterior scleritis: an unusual adverse reaction to influenza vaccine. Br J Rheumatol. 1997;36(1):120–3.View ArticlePubMedGoogle Scholar
  23. Katzav A, Faust-Socher A, Kvapil F, Michaelson DM, Blank M, Pick CG, et al. Antiphospholipid syndrome induction exacerbates a transgenic Alzheimer disease model on a female background. Neurobiol Aging. 2011;32(2):272–9. doi:10.1016/j.neurobiolaging.2009.02.007.View ArticlePubMedGoogle Scholar
  24. van Assen S, Elkayam O, Agmon-Levin N, Cervera R, Doran MF, Dougados M, et al. Vaccination in adult patients with auto-immune inflammatory rheumatic diseases: a systematic literature review for the European League Against Rheumatism evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases. Autoimmun Rev. 2011;10(6):341–52. doi:10.1016/j.autrev.2010.12.003.View ArticlePubMedGoogle Scholar
  25. Vera-Lastra O, Medina G, Cruz-Dominguez Mdel P, Jara LJ, Shoenfeld Y. Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld’s syndrome): clinical and immunological spectrum. Expert Rev Clin Immunol. 2013;9(4):361–73. doi:10.1586/eci.13.2.View ArticlePubMedGoogle Scholar
  26. Israeli E, Agmon-Levin N, Blank M, Shoenfeld Y. Macrophagic myofaciitis a vaccine (alum) autoimmune-related disease. Clin Rev Allergy Immunol. 2011;41(2):163–8. doi:10.1007/s12016-010-8212-4.View ArticlePubMedGoogle Scholar
  27. Beyer WE, Nauta JJ, Palache AM, Giezeman KM, Osterhaus AD. Immunogenicity and safety of inactivated influenza vaccines in primed populations: a systematic literature review and meta-analysis. Vaccine. 2011;29(34):5785–92. doi:10.1016/j.vaccine.2011.05.040.View ArticlePubMedGoogle Scholar
  28. Manganelli S, De Stefano R, Malandrini A, Selvi E, Frati E, Gambelli S, et al. Bilateral recurrent focal myositis of gastrocnemius muscles after BCG vaccination. Rheumatology (Oxford). 2002;41(9):1074–6.View ArticleGoogle Scholar
  29. Ramirez-Rivera J, Vega-Cruz AM, Jaume-Anselmi F. Polymyositis: rare complication of hepatitis B vaccination. An unusual cause of toxic shock syndrome. Bol Asoc Med P R. 2003;95(6):13–6.PubMedGoogle Scholar
  30. Cowling BJ, Feng S, Finelli L, Steffens A, Fowlkes A. Assessment of influenza vaccine effectiveness in a sentinel surveillance network 2010–13, United States. Vaccine. 2015; doi:10.1016/j.vaccine.2015.11.016.Google Scholar
  31. Kwong JC, Stukel TA, Lim J, McGeer AJ, Upshur RE, Johansen H, et al. The effect of universal influenza immunization on mortality and health care use. PLoS Med. 2008;5(10):e211. doi:10.1371/journal.pmed.0050211.PubMed CentralView ArticlePubMedGoogle Scholar
  32. Thommes EW, Ismaila A, Chit A, Meier G, Bauch CT. Cost-effectiveness evaluation of quadrivalent influenza vaccines for seasonal influenza prevention: a dynamic modeling study of Canada and the United Kingdom. BMC Infect Dis. 2015;15:465. doi:10.1186/s12879-015-1193-4.PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Cheng et al. 2016

Advertisement