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  Hemophilus influenzae Type B (Hib) Immunization
  

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By: Karl-Reinhard Kummer
*Original Gennan title: Zur Impfung gegen Haemophilus influenzae-B (HlB), from Merkurstab 1994; 47: 170-81. English by A. R Meuss, FlL, MTA.

Immunization with Hib conjugate vaccines, above all to prevent acute bacterial meningitis caused by Hemophilus influenzae, type b, but also against other diseases such as epiglottitis, acute otitis media, etc., has been available in Germany since 1990. In the discussion below, the emphasis will be on meningitis.

1) Epidemiology of inflammatory neurologic diseases 

Until recently, Hemophilus influenzae did not have the significance it has since achieved. Ibrahim did not refer to it as causing meningitis in 1926, and in the 1940s (Bamberger, Lust & Pfaundler) and even as late at 1976 (Jawetz et al.) it played only a secondary role. Earlier papers (see Robbins & Schneerson, Fothergill & White, Broome) show that almost all children born at full term had antibodies transmitted via the placenta, and almost all children above 6 years of age had antibodies without ever developing manifest disease.

In Europe, there was no appreciable occurrence of acute bacterial meningitis with Hemophilus influenzae until the 1980s (Windorfer et al.), at present in about 33% of cases. In a population of 100,000 children, 34 will contract an invasive Hib disease per annum (Just et al.). 1 in 649 children admitted to hospital will have invasive Hib disease (Stickl and Averbeck). In Finland the figures are twice as high (Peltola et al.). In the USA, 75% of acute bacterial meningitis cases are due to Hib (Kaplan & Feigin). According to Windorfer et al. (1993), the recovery rate was 85% and there are partial recoveries and fatalities. Infants 6-12 months of age and 1 or 2-year old children are particularly at risk.

It is not known why the incidence is so high in industrialized countries with colder climates: Finland, Sweden, Scotland, Canada and the northern USA. It also appears that original populations are particularly at risk: American Indians, Eskimos in Alaska and Australian Aborigines (Ward et al. 1986, Losonsky et aI., Hansman et al., Luetticke). Apparently ethnic differences exist not only in susceptibility to the disease but also in reaction to immunization: Vaccination yields poor immunity for American Indians and Alaskan Eskimos (Siber et al., Ward et al. 1986).

Little note is taken of the fact that all inflammatory diseases of the nervous system are on the increase. This is evident from the paper by Windorfer et al. (1993) who did a poll of pediatric hospitals and units in Bavaria from 1980 to 1990. The number of bacterial meningitis cases showed a slight but steady increase in those years. Virus encephalitis presented major annual variations, with the incidence definitely rising.

In the former GDR, records were kept of CNS infections, with distinction made between "epidemic meningitis" and "viral meningitis and viral encephalitis." Viral encephalitis in particular showed annual variations in incidence from year to year, but with a definitely rising trend. In Table 1, figures are shown for 5-year periods, to give a clearer picture.

Table 1

Frequency of CNS inflammatory diseases in the GDR (annual means, based on statistical yearbook).


2) Aspects to gain insight into meningitis and encephalitis

A comprehensive study of infectious diseases should include consideration of the true, deeper causes. Thus Steiner (1920b) said that lower organisms only find a suitable soil in the human organism if the essential primary conditions have been created. Infection is a sequel, therefore, and not the key process.

The breathing rhythm normally establishes the border between above and below, continually maintaining the balance between processes that take place above and those taking place below. Steiner compares this rhythmic process with a "diaphragm”. The breathing rhythm is embedded in a vast number of other rhythms, e.g. the alternation between waking and sleeping. If those rhythmic functions are stable, the individual has relatively low susceptibility to external factors. Disruptions of the rhythmic quality, and these are almost the norm today, make us susceptible to "insult". Typhoid fever is an example of pathological predominance of upper principles in the digestive tract, diphtheria of lower principles predominating in the upper human being (Steiner 1920b). The reactive responses are called "animal-like" by Steiner. Conditions may develop in the upper human being that are favorable for "small plant-animals". Bacteria, "plant-animals" evolved from an intermediate stage between plants and animals, have a tendency to become animalic, relating to proliferation, metabolism and the blood. They are thus on the anabolic side.

When hardening, mineralizing, plant-like processes become too powerful on one side, "hardening of the lung," typhoid processes and viral infections develop. Viral infections characteristically tend towards catabolism and degeneration, e.g. in cytotoxic reactions. The inflammatory aspect of viral processes is no doubt secondary. Zur Linden (1955, 1960 and 1962) pointed out that virus diseases have an affinity for nerve substance. According to him, bacterial and viral processes need to be seen as quite distinct, and it is wrong to combine them under the umbrella term "pathogen." Another property of viral diseases is the appearance of skin eruptions. The skin, like the nervous system, derives from the ectoderm. Bacteria, on the other hand, prefer the blood route and affect the meninges because they are hollow organs.

Steiner (1920a) considered hydrocephalus in the context of the inversion processes and development of the brain in childhood, when a continual struggle takes place between hydrocephalus and its opposite. A pendulum swing occurs between normal, physiological opposite extremes, as Kienle has shown. Steiner warned against premature removal of the latent tendency to hydrocephalus in infancy, as this would lead to premature aging. If processes such as hydrocephalus in the present case shift to another part of the body, local diseases such as pneumonia develop. Shifting the hydrocephalic process to the serous membranes located at the highest point in the human body would be equivalent to inflammatory diseases of the investing structures of the nervous system. The classic form of bacterial meningitis, e.g. pneumococcal meningitis, presents the image of convexity meningitis, which resembles that of pleuritis.

In childhood we see a predilection for CNS infections. According to Steiner (1920b) the "combined activities of the upper and lower human being, including the mediating rhythmic activity" must be completely different in childhood than later on in life. A child's thoughts are not conscious. The unconscious thought activity of a child enters into the organism and comes to expression in growth and the development of form. Walter takes this further: "Thus it is in the nature of a child, who experiences the environment more as if in sleep or in a dream, to be subject to epidemic diseases." As the powers coming from the head intervene so strongly in the child's body, a child must have "great powers of resistance" to much that evolves in the abdomen. Under certain conditions the child must develop special resistance to those influences from the abdomen. "This desperate use of powers that really should not be used to such an extent in the child's upper organization, results in epidemic cerebrospinal meningitis." "Due to the fact that such an effort made in the child's upper organization, inflammatory changes simply have to develop in the upper organs, the meninges of the spinal cord or the brain, with the other phenomena the inevitable consequence."

According to Steiner (1923a), one reason for the susceptibility of child is the iron process, an extended waking-up process in the course of life. The iron process is weak in children, as is also evident from the low iron levels of mothers' milk, and grows stronger as life goes on. The metabolic process, which is directed upwards from below and to which human beings are always exposed, creates a pathogenesis arising from the lower organism. "Iron normalizes all excessive influences of the one process on the other."

Influenza, poliomyelitis and encephalitis are due to weakness of I rhythmic organization, especially the head-chest rhythm and the breathing rhythm (Steiner 1920a and b), and it is particularly important for heart and head to be in balance (Steiner 1919). If the balance is upset, this "damages the head-chest rhythm" (Steiner 1920 and 1922). This results in sensitivity to external insults, which Steiner refers to as a "constitutional disposition to develop influenza." Encephalitis and poliomyelitis are seen as sequels, at they may take different courses: encephalitis affects the brain as the organ of conscious awareness, poliomyelitis the locomotor system.

A characteristic feature are the sensory disturbances preceding influenza. Ordinary influenza arouses "diseases that actually lie dormant." "The primary aspect is paralysis of the sensorium, and a relationship exists here to sleeping sickness. Progress is made each time we succeed in getting the sensorium properly coordinated - as with Dr Noll's influenza remedy: (Infludo, author), but we have to watch out for secondary conditions that develop whilst the influenza is subsiding .... The ether and physical bodies are put out of action because ego and astral body are lifted out, specifically in the head: inactivation of the sensorium ... "

Treatment strategy must be to activate the will strongly throughout the organism, which is achieved with phosphorus as a medicament. Inactivation of the sensorium is cancelled out by phosphorus, to the point where a tendency to inflammation of the cerebral fluid develops, so that the medicines Steiner suggested for treating pneumonia, meningitis and encephalitis all contained phosphorus and iron as basic constituents, though for different reasons: Phosphorus involves the whole of the rest of the system. The physical body can be brought together with astral body and ego. "With phosphorus, we bring the will into all parts of the organism, we bring in more will."

Encephalitis affects mainly the cerebellum and the midbrain, as Steiner pointed out. This is the case, for instance, with encephalitis following varicella, the incidence of which has distinctly increased in recent times (Windorfer et al. 1993). The changes in mood that follow encephalitis must be regarded as due to midbrain disorder. This explains why Steiner suggested using preparations made of the lamina quadrigemina and the cerebellum to treat encephalitis. He recommended soda baths to revitalize the nervous system (see Walter, p. 9, Steiner 1923a).

The decrease in pneumococcal meningitis and increase in Hib meningitis suggest a change not merely of pathogen but in the character of diseases affecting the nervous system: classic convexity meningitis has been replaced by primarily toxic menigitides of the menigococcal variety. Haemophilus meningitis and meningococcal meningitis have both the typical meningitis characteristics and those of encephalitis, which places them somewhere between the classic bacterial meningitis and encephalitis: Both affect mainly the basal parts adjacent to the midbrain. There is marked neurotropism, with nerve substance directly involved, and there need be no actual spread from the meninges. The influenza-like prodromal stage (see Stehr 1990) may be followed by fulminant development via the blood. Stehr (1990) states that erythrocytes may be attacked directly. Characteristics are the primary lesions of endothelial cells and disruption of the blood-brain barrier (Patrick et al.). The brain's homeostasis for sugar and salt metabolism is upset. In serious cases, consumption coagulopathy develops in septic shock, a kind of "disintegration of the blood" as the physical correlate of the ego organization. With Hib meningitis, Waterhouse-Friedrichsen syndrome may develop (Stehr 1990). This would be comparable to viral skin eruptions.

Another perspective opens up if comparison is made with childhood diseases. These originate in "areas of the body ... where head and trunk join." (Koenig 1959). This applies to the skin eruptions, varicella, mumps diphtheria, etc. Hib infection also tends to begin in the throat, a hypertrophy of digestive processes (Steiner 1920b). Spread is hematogenic, reflecting a bacterial process, and the nervous system is affected in a way seen with viral infections. With meningitis and other invasive infections, the lower human being governs the situation and not the upper human being, as in childhood diseases. With epiglottitis, a situation similar to diphtheria develops rapidly, an infiltration of the ego. Stridor, anxiety and restlessness as psychological aspects are more powerful than the penetration of the body seen with childhood diseases. Invasive infections thus present as a caricature of childhood diseases.

Steiner (1923b) spoke of the importance of warmth. Human beings must penetrate the different temperature levels of the outside world with their own warmth. In the case of influenza, encephalitis and poliomyelitis, the process is upset, as with a "cold," and this results in disposition towards the disease. The same holds true for warmth in the social process, as Steiner has shown (1923b). Streicher gave the example of the "cold" that provided the constitutional basis for President F. D. Roosevelt's poliomyelitis.

The diseases called "influenza, encephalitis and polio" by Rudolf Steiner may be ascribed to strain on the nervous system. Steiner made countless suggestions in the field of education, warning teachers not to lay the foundations for future ill-health by wrong educational measures. The increase in virus diseases may be seen to relate to the mineralizing tendencies in the environment. Husemann and Wolff saw connections between the rising incidence of measles encephalitis and increased exposure of the nervous system to environmental factors, especially continual excitation of the senses. Thus the incidence of cerebral symptoms with common infections has increased, e.g. with viral gastrointestinal infections or Salmonella enteritis. The rising incidence of borrelia meningitis is another sign that the nervous system is increasingly susceptible in childhood.

Steiner also made repeated reference to the role of nutrition. He compared the general degeneration of plants with that of plants growing in soil containing traces of lead (1923a). General environmental intoxication with heavy metals has now become a reality. Steiner (1923a) spoke of the importance of milk plants in the prevention of poliomyelitis, explaining the connection between this and mothers' milk. Takala and Clements quoted numerous investigations showing that breast-feeding provides some protection against Hib meningitis.

Hemophilus influenzae had developed a high degree of resistance to ampicillin in the past (see Kaplan and Feigin, Stehr 1990). The increased incidence of Hib meningitis could be the consequence of the world-wide, uncritical, antibiotic abuse for which there are also no good scientific reasons.

3) Immunization against Hib

Attempts to produce vaccines based on the antigen component of capsular polysaccharides from bacteria started in the 193Os. The first vaccines to be developed were against pneumococcal infections. With the advances made in antibiotic therapy, those particular efforts were not continued. Later vaccines were made by combining a number of capsular polysaccharides. The vaccines conferred little immunity, however. It is interesting to note that vaccination was hardly successful if given prior to the 2nd or 3rd birthday, and vaccines only became fully effective after the 9th year of life. Infants cannot develop immunity to Hemophilus and may be said to be blind to the pathogen, and in the same way polysaccharide vaccines only appear to become effective as the ego matures.

Vaccine efficacy increased considerably when the polysaccharide antigens to Hemophilus influenzae were conjugated with the protein antigens to tetanus or diphtheria toxoid. With this, the vaccines were as effective in infants as in older children (review in Meyer and Gahr). This trick used in vaccine production must, however, be seen as a form of “poisoning.” It enables infants to develop the specific immunity which otherwise is reserved for a later time in life. It is not yet known if this premature development has disadvantages in other areas. Nor have potential consequences for the nonspecific immune system been established so far.

The immune response to conjugate vaccination is high. Almost 90% of children are immune after 3 vaccinations given in infancy, almost 100% after 4 vaccinations (Eskola, Peltola, review by Zielen et al.). According to Stickl (1991), the efficacy of the vaccination is greater than expected for the number of doses given, and immunologists have not so far been able to explain this. However, the duration and quality of protection compared to natural immunization still have to be established. A recent paper by Sitzmann and Jagusch includes critical comments.

The consequences of the Hib immunization campaign may be assumed to be similar to those stated by Albonico et al. for measles, mumps and rubella, i.e. there are doubts about the duration of protection. The first gaps are already appearing in nest protection against measles for children who mothers had only been immunized (Pabst et al.). Regular re-immunization would appear to be necessary, and Germany’s Immunization Commission has recently recommended it for MMR immunization (Stiko). The same may apply to pertussis immunization (Jenkinson). As to the consequences of booster shots, we can only guess (see Albonico et al.). Adult tolerance of the Hib vaccine is not known. Invasive Hib diseases in adults may result if occult immunization is reduced by immunization or inadequate re-immunization and gaps appear in the protection of the total population. This is known to have happened after mass immunization for measles. The disease develops at increasingly less favourable times of life (Stickel 1986/87). This inevitably means more complications, and the situation may be expected to be similar for Hib diseases.

The effect of immunization on the infection spectrum is justifiably stressed (Peltola et al.). However, it is important to consider if, which a disease the incidence of which has increased only relatively few years ago, further changes in pathogen may not bring the reduction in Hib meningitis to nothing. Falle et al. from the Oxford area and Enders in Stuttgart refer to recent increases in pneumonia and otitis caused by noncapsular Hemophilus bacteria. Considering the changes pathogens hav shown in the past, the possibility cannot be excluded that invasive infection with noncapsular Hemophilus bacteria may be on the increase and immunization may prove a failure.

Nor has there been any proof that an immunization procedure that confers protection on some individuals will have a positive effect when applied to large populations. Individual immunization means that a carefully considered decision is made in a given case. Efficacy must inevitably be higher in that case than with immunization given without specific indication to the population as a whole. It is possible that mass immunization programs will not cover some of those who belong to the at-risk groups.

At this point it is important to remember that mass measles immunization failed to achieve its major aim. The incidence of measles encephalitis did go down, but this reflects mainly the absence of mild cases. The number of serious cases resulting in defects did not go down (Koskiniemi and Vaheri).

Immunization against Hemophilus influenzae would have to address a general trend in morbidity, for the incidence of CNS infections has increased both absolutely and relatively in the last 40 years (see Windorfer et al. 1993 and GDR statistical yearbook). Changes in the disease spectrum are common. Bacterial infections, including tuberculosis, have been on the decrease for a long time, in the case of whooping cough and diphtheria even before vaccination was introduced (Wolff). In some instances they actually increased in the years when vaccination started (Buchwald). A similar conclusion may be drawn from a graphic presentation relating to Hib immunization published by Black and Shinefield. Stollermann referred to Danish sources according to which rheumatic fever has shown continual regression from 1860, only increasing during the Second World War. Cyclic variations are, of course, also possible, as in the case of diphtheria, whooping cough (Fine and Clarkson, Fleming et al.) and scarlet fever (Wolff).

It may be assumed that in the case of small infants nest protection meant that immunization would be less effective (Fothergill and Wright, and Kulinska and Kilian, quoted by Stehr 1990). The work of Booy et al. also shows that infants respond less well to immunization. They found that DTP and Hib immunization at 2, 3 and 4 months resulted in lower antibody levels than immunization at 3, 5 and 9 months. In the author's view, relatively little attention is given to the reversible encephalopathy of infants immunized against DPT or DT, polio and Hib at about 3 months. It is possible that the pertussis component is responsible for this (Stickl 1991). Another possible reason may be that the combination of so many vaccines given on one and the same day makes too great a demand.

Side effects of Hib immunization appear on the body boundaries: aggravation of eczema, local reactions, skin eruptions, neuritis, rheumatoid arthritis or epileptic reactions (Stickl 1991). Potential pathogenic effects of the vaccines are at most a matter of conjecture. Invasive bacterial infection following DTP immunization has not been recorded (see Wiersbitzky et al.) The immunization does not exclude the presence of organisms (Stickl and Averbeck). Up to 10% of children of up to 6 years of age may show Hemophilus influenzae in throat swabs (Aniansson et al.). Other authors report elimination of Hemophilus bacteria from the respiratory tract (Takala et al. 1991).

Little reference is made to the relationship human beings have to their bacterial flora at the level of the superficial immune system. Zur Linden (1955 and 1960) put forward the hypothesis that humans live in symbiosis with bacteria and viruses: bacteria in the gastrointestinal tract and viruses in the sphere of the nervous system. This way of thinking is widely accepted for the gastrointestinal and urinary tracts (e.g. Sonnenborn & Greinwald, Mannhardt). As a rule it does not go beyond thinking in terms of friends and enemies for humans and their environment. Psychological aspects are not taken into account. On the other hand immunization is advocated for "social medical" reasons (Luetticke, Pilars de Pilar, Robbins & Schneerson), which fails to take account of the real situation. Thinking as to whether Hib immunization given as yet another injection causes too much stress (Lewis) is also too limited a view.

The overwhelming impression is that the view taken of the facts is too short-sighted. Immunization gives a false feeling of security, at the same time increasing fear of the diseases it is meant to prevent. Anxiety and stress are major contributory factors in the deterioration of immune situations, something that has been known for a long time. It is more difficult to arrive at a positive statement concerning psychological elements with a potentially positive effect. Steiner (1924b) said that the climate of fear, which also lies behind immunization campaigns, must be reduced and transformed into love.

How little we know about these things is borne out by the fact that potential allergization to pollen at the fetal and neonate stages has only recently been confirmed (Pilz). Stickl (1990), who himself was actually in favor of immunization, has provided further examples: Triggering of diseases by exposure to light or the disruption of biological rhythms. 1n spite of this, long-term sequels of immunization are hardly discussed. A complete study of invasive Hib infections must include investigations as to why affected individuals develop the invasive infection rather than immunity. Only the analysis of individual cases, apparently not yet available, will make it possible to take specific measures for the small population that is at risk from invasive Hib diseases.

4) Conclusions

As Albonico et al. demanded, every child and every situation has to be considered individually. The responsibility of deciding for or against immunizing a child lies with the parents. Full information and advice are essential. Changes in environmental conditions and in the constitution as regards health must be taken into account. Many anthroposophical physicians will therefore immunize against poliomyelitis, in spite of zur Linden's arguments of 30 years ago. Physicians who do not follow the conventional immunization schedules do, however, run the risk of being accused of ignorance. A study by Langkarnp and Langhough showed that physicians with long experience tended to be more cautious in giving DTP immunization than the official guidelines. This was interpreted as lack of knowledge.

The author would immunize a child against Hib if the parent's anxiety did not decrease with counseling. He would, however, advise a 4-week interval from other immunizations and not give any other vaccine on the same day. It will also be necessary to take additional measures to improve general health. The "negative concept" of immunization against certain diseases must be part of a strategy including measures to improve the health of children, for instance special attention given to warmth metabolism.

Summary

Hemophilus influenzae has become one of the most important organisms in acute bacterial meningitis over the last 20 years. According to the literature, immunization is effective, but there are questions. The increased incidence of Hib infections is part of a current, possibly secular trend in which infectious diseases of the CNS are on the increase. Steiner's concepts of meningitis, encephalitis and poliomyelitis help us to understand the increase in encephalitic involvement. This suggests approaches to treatment and prevention. The successes reported for immunization may be short-lived, as there is the possibility of pathogen mutation, change of pathogen, or cyclic variations in morbidity. All this makes it imperative to use measures that improve immunological competence.

Addendum

A recent paper published in the USA documents efficacy of Hib immunization (Schoendorf et al.). Following introduction of the immunization, the number of children admitted to hospital and fatalities due to Hemophilus influenzae type b has shown a marked decrease, whereas comparable figures for Streptococcus pneumoniae and Neisseria meningitidis have stayed the same. Unfortunately the paper does not say if the total acute bacterial meningitis morbidity has also gone down. Nor does it invalidate the other arguments against Hib immunization.

Karl-Reinhard Kummer, M.D.

Jaegerstr. 19

D-76227

Karlsruhe Germany

I am greatly indebted to Drs Friedwart Husemann, R. Madeleyn, and G. Soldner for their helpful critical comments.

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