Letter from America: Dr Allan Cunningham: Kawasaki Disease and its causes: March 15th
KAWASAKI DISEASE: “ONE OF PEDIATRIC MEDICINE’S GREATEST MYSTERIES”
Dr. Jane Burns has been looking for the cause of Kawasaki disease for over 40 years. She is the pediatrician who heads a multidisciplinary team at the Kawasaki Disease Research Center at the University of California San Diego. Their search is now more urgent than ever because of a recent upswing of the disease in Japan and the US. (“Pursuing a Pediatric Mystery” Baumgaertner, NY ScienceTimes, 27 February 2024)
KD was first recognized in Japan in 1960, first described in the journals in 1967, and was first reported in the US in1974. (“A New Infantile Acute Mucocutaneous Lymph Node Syndrome (MLNS) Prevailing in Japan” Kawasaki et al, Pediatrics 1974;54:273) It is an immune-inflammatory disease, mainly in young children, that damages the coronary arteries in up to 25% of cases. About 1% of untreated children die. Coronary disease and myocardial infarctions can occur years after recovery from the acute illness. The cause is unknown, but since 1960 the frequency of KD has marched upward worldwide, right along with the expansion of immunization schedules. (“History of the worldwide emergence of Kawasaki disease” Burns, Int J Rheum Dis 2018;21:13… ”Reality of Kawasaki disease epidemiology” Kim, Korean J Pediatr 2019;62:292)…KD has been linked to several vaccines in clinical trials and case reports, including DPT, hep B, hep A, rotavirus, group B meningococcus, yellow fever, pneumococcal conjugate, and influenza vaccines. (“Kawasaki disease and immunization: A systematic review” Phuong et al, Vaccine 2017;35:1770) However, it is taboo to suggest that vaccines could be causal factors. Vaccines are not mentioned in the ScienceTimes article, which focuses on infections and the weather…Fewer than 1% of KD cases are reported to VAERS https://www.bmj.com/content/340/bmj.c2994/rapid-responses even though it is a rare and serious disease of unknown cause in intensively vaccinated young children.
Japan has documented a progressive increase in Kawasaki disease since 1970, with a sharp upswing after 2010 in children 6 months to 5 years of age. (“Age-Dependent Variations in Kawasaki Incidence in Japan” DeHaan et al, JAMA Network Open, online 6 February 2024) This upswing correlates with several additions to Japan’s immunization schedule: In 2010 the routine schedule for children under 6 included OPV, DTaP, BCG, measles, rubella, and Japanese encephalitis vaccines. After 2010 the two OPV doses were replaced by four IPV doses and, in succession, Hib, PCV13, varicella, hepatitis B, and rotavirus vaccines were added to the routine schedule. (“Vaccine chronicle in Japan” Nakayama, J Infect Chemotherapy 2013:19:787… ”Changes in vaccination administration in Japan” Nakano, Vaccine 2023;41:2723) A similar KD increase has been documented in US children between 1979 and 2016. (“Long-term Incidence of Kawasaki Disease in a North American Community: A Population-Based Study” Taslakian et al, Pediatr Cardiol 2021;42:1033)
In 2020 there was a substantial drop in the frequency of KD in the US and Japan following pandemic lockdowns, along with a drop in pediatric respiratory infections, suggesting a role for the infections. (“Incidence of Kawasaki disease before and during the COVID-19 pandemic: a retrospective cohort study in Japan” Iio,BMJ Paediatrics Open 2021;5:001034…”Incidence of Kawasaki Disease Before and After the COVID-19 Pandemic in Japan” Ae, JAMA Pediatr 2022;176:1217. ”Epidemiological and Clinical Features of Kawasaki Disease During the COVID-19 Pandemic in the United States” Burney, JAMA Network Open 2022;5(6):e2217436) Not mentioned was a drop in vaccine uptake during this period. The number of DTaP and MMR doses given to US children under 6 dropped over 60% in March 2020 and had not fully recovered over 6 months later. (“Impact of the COVID-19 Pandemic on Childhood Vaccinations” Murthy et al, MMWR, 11 June 2021)
In thinking about vaccines and Kawasaki disease we should remember that vaccines do more than just stimulate an antibody response to the target infections. They have broad and complex effects on the immune system, particularly when several vaccinations are combined within a short space of time. The best known of these effects are the frightening febrile reactions seen after vaccinations in young infants. Less well known are fatal reactions to vaccines. The official position is that vaccines do not cause SIDS, but during the 1970s many pediatricians in the US, the UK and Japan suspected that the whole cell pertussis vaccine (the P in DPT) had a role in SIDS. This was an important driver in the eventual development of the much less reactive acellular pertussis vaccine (the aP in DaPT)…Autoimmune reactions to vaccines are well known and include fatalities from overstimulation of the immune system by multiple vaccinations. (“Vaccines might have contributed to death of Army reservist”
https://www.cidrap.umn.edu
19 November 2003… “Vaccination and autoimmune disease: what is the evidence?” Wraith et al, Lancet 2003;362:1659)…In fact, non-specific vaccine effects may have a profound impact on overall morbidity and mortality in young children. Killed vaccines and toxoids such as DPT, Hib and IPV are associated with increased morbidity and mortality from non-targeted infections, while live vaccines such as BCG, measles and OPV are associated with morbidity and mortality decreases from non-targeted infections. Leading vaccine epidemiologists have estimated that global vaccination programs could reduce global mortality by 1.1 million deaths per year by taking non-specific vaccine effects into account. (“Vaccinology: time to change the paradigm?” Benn et al, Lancet Infect Dis 2020;20:e274…“Vaccine programmes must consider their effect on general resistance” Aaby et al, BMJ 2012;344:e3769) Measles vaccines and a few others are real lifesavers, but because of the potent non-specific effects of vaccines we cannot say if our immunization program as a whole is increasing or decreasing all-cause morbidity and mortality. (https://www.bmj.com/content/355/bmj.i5170/rr Cunningham, 16 October 2016)
Meissner and others have suggested that “superantigens” trigger KD (Ped Inf Dis J, February 2000), and at least one antigen has been identified. (“A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease” Rowley et al, JID 2020;222:158) The source of this epitope-antigen has not been identified, but possibilities include viruses or vaccine components.
Kawasaki disease is a “perfect storm”… Its biology and epidemiology are complex, but the facts we now have tell us that it is a multifactorial disease triggered by infections in individuals who are genetically susceptible and whose immune systems have been primed by one or more environmental factors. Vaccinations should be included in the list of possibilities.
ALLAN S. CUNNINGHAM 15 March 2024 Cooperstown NY 13326 USA