Dear Editor

I read the article by Jefferson[1] with interest. Although they are rare, vaccine reactions do occur and are suspected of having severe consequences.[2-4] It is here suggested that it is mainly those infants who already have somewhat depleted vitamin C stores, who are affected most. We now know that even modest ascorbate depletion is associated with very high blood histamine levels,[5], as shown in figure 1; so any additional histamine due to infection or vaccinations can cause a toxic histaminaemia leading to capillary fragility.

Figure 1. Results of plasma ascorbic acid (reduced form) and whole blood histamine concentrations in the same blood samples from 437 volunteers in Brooklyn, NY (4). A highly significant increase in the blood histamine level was evident when the plasma ascorbic acid level fell below 0.7 mg/100 mL. This comprised 150 of the 437 (34 percent) men and women. Data from Clemetson 1980.

A very simple remedy is suggested. There is no doubt that a vitamin C supplement can be used to prevent the adverse vaccine reactions brought on by increased blood histamine levels, both in animals and in man. We know that vitamin C acts to remove histamine from the blood by converting it to hydantoin-5-acetic acid.

We also know that a dose of vitamin C appropriate for this purpose may be much greater than the usually recommended dietary allowance. Ascorbic acid has been shown to be life-saving when given with vaccines, even in rats, mice, and rabbits, which make their own ascorbic acid in the liver and do not normally need it in their diet. It seems that even these animals do not always make enough ascorbic acid for their own needs.

As for human infants, the appropriate dose of vitamin C to be given with vaccines -- and the best method of administering it -- still need to be determined. Ascorbic acid is not toxic, so I have suggested 500 mg to be given to infants in fruit juice on the day of vaccination. Some authorities may decide to give sodium ascorbate intramuscularly, already prepared with the vaccine.

Much has been written on the specific toxicity of individual vaccines, but histamine toxicity is a general effect. Now that infants receive as many as six vaccines together at eight weeks of age, we have to think of the cumulative histamine increase as a general toxicity. Excellent work on vitamin C and vaccine reactions was done many years ago and was summarized in 1999.[6] The results of all the experiments were consistent and showed that ascorbic acid reduces both the morbidity and the mortality due to all the bacterial antigens studied, and in all the different animals tested.

The observation that borderline ascorbic acid deficiency increases the morbidity and mortality from diphtheria antigen in guinea pigs goes back to work by Harde[7] in 1934 and by King and Menten[8] in 1935, not long after the isolation of ascorbic acid by Svirbely and Szent-Gyorgyi[9] and by King and Waugh[10] in 1932. King and Menten observed that there is a wide zone of vitamin C depletion, without the appearance of scurvy, wherein physiological processes are subnormal and an animal is more sensitive to bacterial toxins.

In addition to providing protection against diphtheria toxoid, vitamin C is also protective against the toxoids of four different varieties of gas gangrene bacteria in mice, as shown by Buller-Souto and Lima[11] in Table 1, and against tetanus toxoid in rats, as shown by Dey[12] in Table 2.

Table 1
Protective activity of L-ascorbic acid 10mg daily, given intramuscularly to mice for 3 days preceding both a single and a double LD50 dose of four different gas gangrene toxins. Note the unsurprisingly good protective activity of ascorbic acid even in mice, which make their own ascorbic acid

AA=L-ascorbic acid; n=number of animals
An LD50 dose of toxin is that previously found to kill 50 percent of the animals
2 LD50 is twice that dose
From Büller-Souto and Lima.[11]. Translated and summarised by Clemetson,[6] reproduced with permission from the Journal of Orthomolecular Medicine

Table 2. Efficiency of vitamin C in counteracting the toxicity of tetanus antigen in adult rats

AA=L-ascorbic acid; MLD=minimum lethal dose; 2 MLD=twice minimum lethal dose; i.m.=intramuscular injection; i.p.=intraperitoneal injection.
Data from Dey.[12] Table reproduced with permission from the Journal of Orthomolecular Medicine.[6]

Fukada and Koyama[13] demonstrated that pretreatment with ascorbic acid (500 mg/day), mixed in a soybean curd diet, protected their rabbits against the toxic effects of Salmonella typhi endotoxin. Ascorbic acid saturation markedly ameliorated the depletion of liver glycogen after endotoxin, both in intact and in adrenalectomised rabbits, and completely prevented the attendant hypoglycaemia.

The seminal studies of Kalokerinos[14] showed that supplementary vitamin C was uniformly effective in preventing infant deaths following vaccination in Aborigine children in Australia.

In view of all these most important and encouraging findings, one wonders why ascorbic acid has not yet been widely recommended for routine use with vaccinations. This reticence may have been due to a sense that such an anti-toxic action could possibly vitiate the purpose of a vaccine. However, now that we know that the anti-toxic effect of vitamin C is due to its role in the removal of histamine and does not affect the antigen, we can recommend it freely. Ascorbic acid acts as a co-enzyme in the elimination of histamine by converting it to hydantoin-5-acetic acid, and on to aspartic acid in vivo.[15] We can recommend vitamin C for general use with all vaccines, without any fear that the vaccine will lose its intended potency as a stimulant of immunity.

The vaccine-ascorbate studies cited here are very old, and many, from abroad. It would be reassuring to hear of any new studies -- not that they would necessarily be any more reliable, but that plasma ascorbic acid and whole blood histamine studies could now be included.

References

1. Real or perceived adverse effects of vaccines and the media - a tale of our times. Jefferson T. J Epidemiol Community Health 2000; 54: 402-403

2. Clemetson CAB. Elevated blood histamine caused by vaccinations and vitamin C deficiency may mimic the shaken baby syndrome. Medical Hypotheses 2004; 62:533-536.

3. Clemetson CAB. Capillary fragility as a cause of subdural hemorrhage in infants. Medical Hypotheses and Research 2004; 1:121-129.

4. Clemetson CAB. Is it "shaken baby," or Barlow's disease variant? Journal of American Physicians and Surgeons 2004; 9:78-80.

5. Clemetson CAB. Histamine and ascorbic acid in human blood. Journal of Nutrition 1980; 110:662-668.

6. Clemetson CAB. Vaccinations, inoculations and ascorbic acid. Journal of Orthomolecular Medicine 1999; 14:137-142.

7. Harde E. Acide ascorbique (vitamin C) et intoxications. Comptes Rendus de l'Academie des Sciences Paris 1934; 119:618-620.

8. King CG, Menten ML. The influence of vitamin C level upon resistance to diphtheria toxin. Journal of Nutrition 1935; 10:129-140.

9. Svirbely JL,Szent-Gyorgyi A. The chemical nature of vitamin C. Biochemical Journal 1932; 27:279-285.

10. King CG, Waugh WA. The chemical nature of vitamin C. Science 1932; 75:357-358.

11. Buller-Souto A, Lima C. Activity of L-ascorbic acid on the toxins of gas gangrene. Memorias do instituto Butantan, Sao Paulo, Brasil, 1939; 12:265-295, in Portuguese; 297-311, in French (same data).

12. Dey PK. Efficiency of vitamin C in counteracting tetanus toxin toxicity. Naturwissenschaften 1966; 53:310.

13. Fukada T, Koyama T. Prevention by ascorbic acid of liver glycogen depletion in endotoxin intoxication. Nature (London) 1963; 200:1327.

14. Kalokerinos A. Every Second Child. Thomas Nelson (Australia) Ltd. 1974. Now reprinted by Falconi O, Box 3345, Saratoga, CA 95070.

15. Chatterjee IB, Majumder AK, Nandi BK, Subramanian N. Synthesis and some major functions of vitamin C in animals. Annals of New York Academy of Sciences 1975; 258:24-47

We read the Letter by Dimoliatis with interest.[1] However, "0.33x50+1.0x(80–50) = 46.5", more accurately, we had to put QALYs = (0.67)x(50y) = 33.5y and DALYs = (0.33)x(50y)+(1.0)x(80y–30y) = 46.5y.

If substitute (80-50) by (80-30) result must be different.

I believe that something is wrong in this short piece intended to add clarity!

Reference

1. Dimoliatis I D K. Qualia years (QY)—not years—should be the unit of measurement of QALYs, DALYs, life expectancy, and life. J Epidemiol Community Health 2004; 58: 1054-1055.

Dear Editor

“The further back you look, the further forward you can see”. These words of Winston Churchill are the compelling reason for backing Berridge and Gorsky’s,[1] and Scally and Womack’s[2] calls for more attention to public health history.

The lessons I have learnt from history are that my work is part of a long tradition, that many others have struggled with the same type of challenges that I confront, and that change requires luck, tenacity, patience and belief. While Hippocrates’ contributions to public health are well known, those of Indian physicians are not. My Indian predecessors Caraka (1st century AD) who said that "concord is health, discord is disease" and Susruta (4th century AD) whose purpose was to prolong life and prevent disease are also worth studying.

The University of Edinburgh has a tradition of public health to be proud of but the story is largely unknown and seldom told. Academics are well placed to be the champions of public health history, and they can take such opportunities as inaugural lectures where the contextual legacy is welcomed.[3]

In the book Concepts of Epidemiology[4] I wrote a section entitled Building on an Epidemiological Education: Role of Historical Landmarks (pp 291-293). The study of the classics,[5] or in Thomas Kuhn’s terminology exemplars,[6] provides inspiration as well as instruction.[4] In my book, I chose Lind and scurvy, Jenner and smallpox and Snow and cholera as my exemplars. Even in the well known stories there are new slants that matter in the modern era. For example, John Snow’s book On the Mode of Communication of Cholera cost him £200 to publish and sold 56 copies in three years, making him £3 and 12 shilling (60p). Learned committees and many of his peers rejected his findings. This year marks the 150th anniversary of the Broad Street epidemic of cholera, and Snow’s famous removal of the pump handle. Those enmeshed in the web of the UK Research Assessment Exercise would do well to reflect on the limitations of peer review and indicators of popularity and attention as a judge of quality in research.

In 2002, Edinburgh University celebrated the 100th anniversary of the founding of its academic department of public health, the Usher Institute of Public Health. Our conference examined the past, present and future of public health, and the proceedings will be published shortly.[7] The celebrants crossed at least three generations of public health practitioners and academics. As part of the centenary events we created a public health walk of Edinburgh. This event centred on public health history, connected the living and now global public health community of Edinburgh students and staff to our deceased, illustrious predecessors to whom we paid respect. I cannot imagine another conference theme that would have such a broad appeal.

JECH’s support of public health and epidemiological history deserves acclaim.

References

1. Berridge V, Gorsky M. The importance of the past in public health. JECH 2004; 258: 728-729

2. Scally G, Womack J. The importance of the past in public health. JECH 2004; 258: 751-755

3. Bhopal R S. Generating health from the pattern of disease. Proc R Coll Physicians Edinburgh 2001; 31:293-298

4. Bhopal R S. Concepts of Epidemiology. Oxford, Oxford University Press, 2002

5. Buck C, Llopis A, Najera E, Terris M. The Challenge of Epidemiology. Issues and Selected Readings. Washington DC: Pan American Health Organization, 1988

6. Kuhn TS. The Structure of Scientific Revolutions. Third ed. Chicago: The University of Chicago Press, 1996

7. Bhopal R, Last J. Public health: past, present and future. London, Nuffield Trust 2004 (in press)

Dear Editor

After a journey to Asia during the SARS outbreak, Syed et al suggested that "the public health significance of such potent symbols as the face mask may be considered in strategies to tackle other emerging infections" [1]. Nevertheless, like other unsolved puzzles of the SARS emergence, the exact impact and lesson learned from this collective and profound symbol of masks wearing is still controversial.

Face mask for SARS prevention - a significant public health strategy?

The dramatic, somehow fearful image of people collectively wearing masks has indeed become a mighty symbol of the SARS epidemic. Syed et al indicated that "though of uncertain protective benefit, the wearing of masks may have contributed to the awareness of the collective and personal responsibility in combating infectious disease". However, firsthand experiences of SARS in affected areas seem to provide a quite different scenario. Already at the beginning of the SARS outbreak, WHO spokesman Dick Thompson warned against making the public wear face masks. He said "people buying them so they feel comfortable riding the subway doesn't make a lot of sense, we're just not going to encourage silliness because we don't want to see a shortage of masks" [2].

In addition to competing to obtain masks with medical workers who really needed them during the crisis, having the people collectively wear masks in all kinds of non-nosocomial environments delivered a strong but exaggerated impression of the SARS risk to the public.

This behavior was interpreted in a lay epidemiological perspective - the chance of getting infected with SARS was virtually everywhere otherwise why would random people wear masks while going to school or work, riding the metro, or leaving home for simply grocery shopping.

The truth was that before the "mask-terror" started, fair epidemiological investigation showed that it was adequate to advise the public to keep their routines as normal as possible because people's routine life wouldn't increase the risk of SARS transmission.

For example, in the early stage of the endemic, WHO epidemiologists maintained the view that asymptomatic transmission doesn't appear to occur [3]. People wouldn't just sit there and release SARS bugs. Canadian health officials also indicated that the chance of contracting SARS in places like Chinatowns was virtually nil [4] and urged the public to stop buying masks in fear of a possible shortage of masks in health care facilities [5].

The risk of SARS infection was definitely limited to the close contacts with SARS symptomatic patients. The close contact, by WHO's definition, was having cared for, lived with, or had direct contact with respiratory secretions or body fluids of a suspected or probable case of SARS [6]. Therefore, the need to wear mask by the general public to reduce the risk was by all means an epidemiological misunderstanding that created enormous fear an d hysteria in Asians countries. In comparison to its counterpart Asian cities, where a mask was considered a must-have and eventually become a symbol of public horror and panic, the Canadian¡¦s transparent and epidemiology-based risk communication assessment probably made Toronto a less panic-stricken city considering that not many people were wearing masks on the streets.

The thought "risk-is-everywhere" best portrayed by mass mask wearing fired up an extreme public panic and impaired disease control efforts in several ways.

Forced to response to the widespread public panic induced by this dramatic and visual "mask-terror" on TV on an hourly base, every public health jurisdiction in SARS affected areas was overwhelmed with unthinkable and cumbersome tasks triggered by the infectious "mask panic". These included finding millions of facial mask in a very short period of time, calling off regular social and economic activities, mass resignation of health workers [ 7, 8], preventing the rejection of seasonal fever patients by some medical institutions in fear of SARS infection or of losing general patients who refused to visit hospitals where SARS patients had previously been found [9].

The epidemiology of fear 'V the unlearned lesson of the SARS outbreak

The importance of the public's reaction to an unknown outbreak or a comparable bio-terrorism attack is critical, especially because it risks creating chaos and widespread mass panic, thus crippling effective responses to the situation. The epidemiology of fear is arguably the most under-learned lesson of last years SARS crisis. Indeed, while a sudden outbreak or a bio-terrorist attack unfolds, in addition to possible biological agents, there is always another equally dreadful infectious phenomenon in the shadows - public panic. The lessons from SARS prove again that unmanaged public panic may be as alarming as the disease itself.

Two lessons learned from Taipei, one of the epicenters of the SARS outbreak last year, reveal some of the possible mechanisms of public panic escalation and how this can be avoided.

The leader's example effect - Taipei's costly lesson

In a crisis, decision makers are tempted to implement draconian measures even in the absence of substantial evidence. Taipei, the last city to be removed from WHO's list of SARS affected area, exemplifies the costly lesson of risk communication within the public. When a patient who had recently visited China was reported ill and further diagnosed as a SARS probable case, leaders of the Taipei city government, including the mayor and the hea d of the health department, started wearing masks at SARS press conferences. They believed that they were thus showing their determination to combat this disease.

Nevertheless, this political posturing of a lineup of well-known leaders wearing face masks in the city hall created an alarming image. This image, once broadcasted through the media, set off an enormous public panic in Taipei. Residents in Taipei felt that the risk of getting infected with SARS was literally everywhere. The "mask-panic" developed when Mayor Ma Ying-jiu ordered every citizen to put on a face mask when ridding the city metro and visiting city hall.

A shocking proposal to compulsory quarantine the whole country¡'s 23 millions people for 10 days gained majority support according to a local poll [10]. This unprecedented "whole nation quarantine" was formally discussed by local politicians and influential opinion leaders. Fortunately, the outbreak faded away almost as promptly as it bloomed. This multi-billion dollar proposal didn't survive. Still, the exceptional

magnitude of Taiwan's compulsory quarantine overwhelmed its SARS affected rivals which reflected its unparalleled mass panic rather than rational reactions. In terms of number of people quarantined per SARS patient found, Taiwan's 227 people quarantined per SARS case [11] largely outnumbered Hong-Kong's 2 to 3 people [12], Singapore's 37 people[13] and Toronto's close contacts oriented, epidemiology-based voluntary quarantine measure.

Social amplification of the risk

We learned from Taipei's experience that disease control measures taken by the health authority helped formulate the risk perception of SARS. The SARS corona virus was invisible, novel and hard to comprehend in a short period of time. But the initial SARS control measures were obvious and magnified in the media spotlight, which helped create the first impressions of SARS, its infection risk, and routes of transmission. The control measures implemented by the Taipei city government included spreading disinfectant on the streets, free distribution of volumes of bleach to nearly one million households, compulsory quarantine of hundreds of thousands healthy people who didn't have any known close contact with SARS patients but simply had visited the hospitals where SARS patients were later found, encouraging politicians and professional health leaders not clinically involved in SAR S patient care to wear masks in public and show this on TV, etc. All of these non-epidemiology based measures helped greatly enhance the public panic toward SARS.

These experiences showed how important it is to respond to an outbreak with prompt epidemiological investigation for both disease containment as well as ease of the escalating public panic. Public health history has shown that in order to fail a disease control effort, health authorities can't do better than stigmatize patients, exaggerate the threat, and horrify the public with measures that have no scientific support.

The Experiences from last year tell us that in facing an unknown outbreak, neither reacting with ignorance like the Chinese authority (SARS was officially found in Vietnam, three months after the first case had surfaced in Guangdong, China) nor responding with paranoia (like WHO's unscientific SARS travel advisory announcements which exaggerated the SARS risk and literally killed local economies) had helped to conquer SARS. The assertion "the only thing we have to fear is fear itself" has never been so accurate as during the SARS crisis. In a word, any outbreak control measure, no matter how fearsome the disease may seem to be, should be based on epidemiological evidences, not fear let alone hysteria.

References

1.Syed Q, Sopwith W, M Regan M, Bellis MA. Behind the mask. Journey through an epidemic: some observations of contrasting public health responses to SARS. J Epidemiol Community Health, 2003; 57: 855 - 856.

2.Tom Cohen. Most don¡¦t need masks to stave off SARS. Associated Press. 11 April 2003.

3.WHO. SARS 'V multi-country outbreak - Update 25. Interim report of the WHO team in China, status of the main SARS outbreaks in different countries. http://www.who.int/csr/don/2003_04_09/en/ (accessed 11 April 2003).

4.CBC News. SARS deals Toronto economic hit. 03 April 2003; http://www.cbc.ca/stories/2003/04/03/sars$030403 (accessed 03 April 2003 )

5.CBC British Columbia. SARS clinic ready for opening. Apr 03, 2003; http://vancouver.cbc.ca/regional/servlet/View?filename=bc_masks20030403 (accessed 10 August 2004)

6.WHO. Case definition for surveillance of Severe Acute Respiratory Syndrome (SARS). http://www.who.int/csr/sars/casedefinition/en/

7.BBC News UK Edition. Mass resignations of health workers in Taiwan are bringing extra pressure on the island¡¦s medical system as a record 65 new cases of SARS are reported. 27 May 2003.

8.CBC News. Some Toronto nurses quit over SARS. 26 April 2003. http://www.cbc.ca/stories/2003/04/26/sarsnurses_030426 (accessed 10 August 2004)

9.Next Magazine Taiwan. Nine SARS tolls undeserved, killed by the lie of the chief of municipal Ho-Ping hospital. Vol. 102. 8 May 2003. (in Chinese)

10.Hong Shu-hui. More than 70% of the respondents agree on the implementation of whole country quarantine, according to a poll. United Daily News. 16 May 2003. http://udndata.com/library/

11.Division of Medical and Outberk Respons, Cabitent¡¦s SARS Committee Taiwan. Report on SARS Contorl in Taiwan (in chinese)

12.Government of the Hong Kong Special Administrative Region. Health, Welfare and Food Bureau. SARS Bulletin. 23 June 2003 http://www.info.gov.hk/dh/diseases/ap/eng/bulletin0517.pdf

13.Sharmiipal Kaur. $2.8m paid to SARS-hit businesses, quarantine cases so far. The straits Times. 15 August 2003 http://www.sars.gov.sg/archive/