Search

In five children neural complications occurred following diphtheria immunization. In two cases, damage was related to the injection (vaccination-induced poliomyelitis), in three cases it could be traced back to a hyperergic reaction to diphtheria toxoid on the cerebral vessels. The latter complication is typical of individuals being immunized against diphtheria. Such complications are extremely rare; by no means can they question the value of active immunization against diphtheria.

In the third year of life of a girl vaccinated neonatally against tuberculosis an abscess of the associated lymph nodes appeared which contained acid-fast bacilli. After extirpation of the lymph nodes weeks later an intestinal BCG-dissemination was observed which seemed to be cured under a brief tuberculostatic therapy. At the age of 22 years a left sided hemiplegia due to aneurysms and thrombosis of 2 cerebral arteries was seen. At autopsy in the adventitia of the arteria basilaris macrophages were discovered which showed intracellular acid-fast bacilli. A paralysis of the oculomotor nerve appearing later was also caused by this brain lesion. Towards the end of a pregnancy a serious BCG-dissemination in the intestines relapsed. A healthy premature child was born. Massive tuberculostatic therapy was inefficient. The woman died in her 27th year of life. A defective function of the macrophages is suggested for the immunological abnormality.

Recent rubella infection (rubella-specific IgM positive, raised rubella complement fixation reaction and haemagglutination inhibition) could be demonstrated during a prophylactic investigation in early pregnancy in a 19-year-old girl previously successfully immunised with Cendehill vaccine (seroconversion). Due to the seroconversion demonstrated during school age no interruption was performed. The newborn baby had a rubella-HAI-antibody titre in the umbilical blood of 1 : 640, but no rubella-specific IgM antibodies (also at later controls). Rubella infection of the child in utero could thud be excluded. This for the first time confirms the protective effect of the Cendehill vaccine in the prophylaxis of rubella embryopathy.

In the third year of life of a girl vaccinated neonatally against tuberculosis an abscess of the associated lymph nodes appeared which contained acid-fast bacilli. After extirpation of the lymph nodes weeks later an intestinal BCG-dissemination was observed which seemed to be cured under a brief tuberculostatic therapy. At the age of 22 years a left sided hemiplegia due to aneurysms and thrombosis of 2 cerebral arteries was seen. At autopsy in the adventitia of the arteria basilaris macrophages were discovered which showed intracellular acid-fast bacilli. A paralysis of the oculomotor nerve appearing later was also caused by this brain lesion. Towards the end of a pregnancy a serious BCG-dissemination in the intestines relapsed. A healthy premature child was born. Massive tuberculostatic therapy was inefficient. The woman died in her 27th year of life. A defective function of the macrophages is suggested for the immunological abnormality.

The immunogenicity and reactogenicity of the Urabe Am 9 mumps virus vaccine strain were studied after the administration of different doses of the vaccine to 197 children ranging in age from seven and a half months to nine years and without a history of mumps. There was no effect of dose on the response in serum neutralizing antibodies in the range of 10 2·9 to 10 4·7 TCID 50 /dose. In the 90 subjects without detectable serum neutralization antibodies before vaccination seroconversion was obtained in 94·4% after 42 days. Half of a group of 34 seropositive children who were tested also showed a fourfold or greater rise in antibodies. Persistence of vaccine-enhanced haemagluttinin-inhibition (EHI) antibodies was satisfactory as only two of 46 vaccinees followed-up for between 27 and 32 months had undetectable levels of EHI antibodies and the geometric mean titre of vaccine-induced EHI antibodies had only fallen to about one-third by 32 months after vaccination. Although there was serological evidence of a subclinical re-infection in three subjects, to date none of the vaccinees has had clinical mumps indicating that the vaccine confers protection against disease. The vaccine was well tolerated. Furthermore, the majority of the few ‘reactions’ reported were probably not vaccine-related. It is concluded that the Urabe Am 9 is an acceptable strain for use in live mumps vaccines.

In the haemagglutination inhibition (HI) test, 20 cervine sera, most of which came from Northern Germany, were treated with receptor destroying enzyme (RDE) and 11 sera were found to contain antibodies against the H1N1 (A/USSR 90/77) and H3N2 (A/Victoria 13/75, A/Texas 1/77) influenza viruses. Only two sera contained antibodies against H3N2 viruses, and seven sera were negative. Evidence of the specificity of influenza antibodies was provided by the following findings: 1) the IgG serum extracts showed the same inhibitory activity of haemagglutinin as the RDE treated sera; 2) addition of protein A led to an increase in the HI titers; 3) in the haemolysis in gel test, some of the HI positive sera formed haemolysis rings of the same diameter as hyperimmune antiinfluenza A (H1N1) serum; and 4) the cervine sera reacted positively in the neuraminidase inhibition (NI) test. It is remarkable that influenza H1N1 antibodies were found in the serum of one cervine before this virus strain appeared in humans.

The rare occurrence of rubella embryopathy in Mali stimulated us to investigate the rubella immunity of the population. Sera from females from Hamburg (n = 97) between 16 and 42 years old were in 84,5% seropositive (hemolysin-in-gel test) whilst a sample of Malien females (n = 99) were positive in 92,9%. Our investigations showed that the Malien children were significantly (p = less than 0.001) earlier infected by rubella than in Hamburg (Mali: children under 8 years [n = 196] in 46.9%; Hamburg [n = 151] in 20.5%). In Mali 7-8 years old children were already in 87.5% seropositive (Hamburg: only in 46.7%). The early immunity in childhood is due to the bigger African family in comparison with the smaller European family. The height of rubella serum titers was in grown-ups identical, but the relationship was vice versa in both studied newborn populations. Newborns from Mali showed lower rubella antibody titers than their mothers (newborns from Hamburg had a tendency to higher titers). Similar relationships were found already in the amount of neutralizing polioantibodies in newborns from both countries. A rubella immunisation in Mali seems not to be indicated.

Conventional vaccinia strains were cultured at different temperatures, because it is known that vaccinia viruses which are human pathogens grow even at higher temperatures (41 degrees C). Neither the vaccination strains nor the vaccinia viruses which were isolated from vaccination vesicles after normal (n equals 7) or abnormal primary vaccinations (n equals 2) multiplied at higher incubation temperatures; Vaccinia viruses isolated from CSF of four patients with neurological complications behaved differently. Uninhibited growth at 41 degrees C (with high infection titres) suggest that the viruses isolated from CSF were vaccinia variants with abnormal characteristics. Accordingly, these variants morphologically formed plaques in Vero-cell cultures which were two to three times larger than those of vaccinia viruses obtained from CSF of primary vaccinated cases after only moderately severe general reactions, and which on temperature test responded like the viruses used in the original vaccination.

Die Frage, ob das Impfrisiko unter den heutigen Bedingungen groser ist als die Risiken einer Pockeneinschleppung, wird anhand der Erfahrungen mit Variola-Einbruchen in die BRD analysiert. Als Parameter wurden Todesfalle durch Pocken bzw. im Gefolge von Pockenimpfkomplikationen gewahlt. Unter Berucksichtigung der gegenwartig noch labilen Seuchensituation in den Pockenendemiegebieten mus bei Einstellung der Pockenschutzimpfungen eher mit einer etwas hoheren Quote an den genannten todlichen Zwischenfallen in der BRD gerechnet werden.

Der Impfschutz eines Kollektivs kann durch Nachimpfungen mit wirksamen Impfstoffen, in hoherem Mase durch Analyse der Pockenfestigkeit im Endemiegebiet gepruft werden. Mit Pockenimpfstoffen entsprechend den Empfehlungen der Weltgesundheitsorganisation sind beim Erstimpfling in nahezu 100% Pusteln und beim zwolfjahrigen Wiederimpfling in 80 bis 90% Blaschen- oder Pustelreaktionen („major reactions”) und damit ein Impfschutz zu erzielen. Knotchenreaktionen („equivocal reactions”) mit obigen Impfstoffen fuhrten bei 755; Probanden in 62% zu einer Virusvermehrung und somit zu einer Auffrischung des Impfschutzes. Im internationalen Reiseverkehr kann aber nur bei Blaschen- und Pustelreaktionen mit der notwendigen Wahrscheinlichkeit ein Impfschutz fur etwa drei Jahre angenommen werden. Andererseits ist das Vorkommen solcher Reaktionen nicht unbedingt gleichbedeutend mit einer Anfalligkeit fur Pocken, wie auch aus Studien der Impfreaktionen von fruher an Pocken Erkrankten hervorgeht. Ein Impfschnitt von 1 cm Lange ist bei der Wiederimpfung zu fordern, um die Restimmunitat entsprechend zu belasten. Dies ist vor allem bei Impfungen in der Pockeninkubation von besonderer Wichtigkeit, die nur bis zum sechsten Tag nach Kontakt sinnvoll sind, was anhand von Untersuchungen uber die Entwicklung der Impfallergie aufgezeigt wird. Ein positiver Intrakutantest mit inaktiviertem Pockenimpfstoff bei Geimpften kann mit Einschrankung als Hinweis auf die Existenz eines gewissen Impfschutzes, ein negativer Testausfall mus dagegen als Ausdruck einer Vaccinia- oder Variola-Anfalligkeit gewertet werden. The extent of protection present in a given group can be tested by revaccination with an effective vaccine, but in particular by analysing the stability of smallpox in an endemic area. Using vaccines in accordance with the recommendation of W.H.O., almost all of those vaccinated for the first time had pustular reactions; revaccination after 12 years gave vesicular and pustular reactions (major reactions) and thus full protection in 80—90%. Equivocal reactions with this vaccine in 62% of 755 subjects led to virus multiplication and thus to a renewal of vaccination protection. As for international journeys, only major reactions can with certainty provide protection for about three years. But the occurrence of such reaction is not necessarily indicative of susceptibility to smallpox, as has been shown in studies of vaccination reactions in persons who had had smallpox. A vaccinating cut should be 1 cm. on revaccination in order to provide the necessary booster. This is particularly essential when vaccination is performed within the incubation period of smallpox: it is of use only if done by the sixth day after contact. Positive intercutaneous test with activated smallpox vaccine in those who have been previously vaccinated can with reservations be taken as an indication of certain protection, while a negative test must be interpreted as susceptibility to vaccinia or variola. Reacciones vacunales y vacunacion antivariolica La inmunidad vacunal de una colectividad puede probarse por vacunaciones posteriores con vacunas activas y en mayor medida por el analisis de la estabilidad de la viruela en las zonas endemicas. Con las vacunas recomendadas por la organizacion mundial de la salud se pueden lograr pustulas en cerca de un 100% en los sujetos vacunados por primera vez y reacciones vesiculosas o pustulosas ("major reactions") en un 80 a 90% en los revacunados de doce anos, y con ello una inmunidad vacunal. Las reacciones papulosas ("equivocal reactions") con las vacunas mencionadas condujeron en 755 probandos, en un 62%, a una multiplicacion virasica y, con ello, a un avivamiento de la inmunidad vacunal. En el trafico internacional de viajeros solo se admite, sin embargo, una inmunidad vacunal para unos tres anos en las reacciones vesiculosas o pustulosas con la necesaria probabilidad. Por otra parte, la aparicion de tales reacciones no es necesariamente identica a la susceptibilidad a la viruela, como se desprende de los estudios antiguos de las reacciones vacunales en enfermos de viruela. Una incision vacunal de un cm de longitud se ha de exigir en la revacunacion, con objeto de cargar adecuadamente la inmunidad residual. Esto es de especial importancia, sobre todo en las vacunaciones durante la incubacion variolica, que solo tienen sentido hasta el sexto dia del contacto, lo que se muestra a base de las exploraciones sobre el desarrollo de la alergia vacunal. El test intracutaneo positivo con vacuna antivariolica inactivada en vacunados puede valorarse, con limitaciones, como indicio de la existencia de una cierta inmunidad vacunal, y el negativo tiene que valorarse, por el contrario, como expresion de una susceptibilidad a la viruela o a la vacuna.

Zwei Falle von Impfblatternrezidiven 43 resp. 142 Tage p.v. wurden mitgeteilt. In einem dritten Fall traten wahrend eines Infektes uncharakteristische ‚'Granula“ an der alten Impfnarbe auf, so das der Verdacht auf eine vaccinale Genese bestand.

Sera from patients with typical cutaneous or general allergic reactions and other complaints after application of non-infectious smallpox vaccine have been examined for precipitating antibodies against calf serum and its albumin- or globulin-fraction respectively. Out of 12 patients with typical allergic reactions resembling Arthus-phenomenon or serum sickness, sera from seven of them reacted positively against whole serum and all but one of these to serum globulin. Also, no such antibodies were detected in a group of persons with less typical clinical signs. No antibodies against host tissue or the virus contained in the vaccine were detected by the microtechnique used, antibodies against calf serum albumin were found only in one patient. The possible role of calf serum contamination of viral vaccines for evoking allergic reactions in sensitized persons is discussed briefly.

The occurrence of OC-43 coronarvirus-like infections in the population of Hamburg was determined by a monthly serological survey (hemagglutintion inhibition test [HI]) undertaken between October 1974 and October 1976. Studies of 3,016 sera revealed a high incidence of HI antibodies (58,2%). The frequency of seropositive reactions (= 1:8) and the geometric mean titer were higher in individuals 15 to 24 years old. Treatment of 50 postive sera (titer 1:16 -1:64) with receptor destroying enzyme, kaolin and ethacridin for elimination of nonspecific inhbitiros did not modify the HI-titer of the investigated sera. The serological seasonal pattern suggests that coronaviruses are circulating the whole year in the urban population with a prevlence in the fall-winter period. Of the 331 paired sera examined, 6.6% presented a four- to eightfold rise intiter within eight weeks.

Using the Treponema Pallidum Haemagglutination Assay (TPHA) for the demonstration of treponema-specific antibodies, 444 children in age groups between 5 months and 10 years from different parts of Mali (Africa) were investigated for endemic treponematoses. The rate of seroreactivity (1,85%) in the age groups under four years (n = 270) indicates a low incidence of treponemal infections. From these observations it can be concluded that treponemal infections in infants are not caused by suckling of the babies on infectious nipples of their mothers. The high rate of TPHA-reactive children (17,8%) in the age groups between 5 and 10 years (n = 174) can be explained by the assumption of nonvenereal transmission of the disease. Furthermore, 101 mothers from Bamako and their newborn babies, were investigated serologically. In 17 mothers (17%) the TPHA was reactive. Treponema-specific antibodies were transmitted to the children in all cases and with nearly identical antibody titres.

The incidence of Chlamydia psittaci infections in Hamburg has been studied using the complement fixation test on 655 human sera collected from patients with respiratory tract diseases. Of the 653 sera investigated, 78 (11.9%) showed antibody titers between 1:8 and 1:128. Of the positive sera, 21 (16.9%) presented values of greater than or equal to 1:32. This infection is encountered more often in individuals over 21 years of age (15.9% to 23.4%) than in persons under 20 (0.8% to 6.0%). General practitioners' attention must be drawn to Chlamydia psittaci infections, since they seem to be of greater importance in human pathology than is generally assumed.

Since the introduction of oral polio vaccine in 1962, 30 cases of convulsions were registered within 30 days after the immunisation in Hamburg. 29 further cases from the surroundings came also to our attention. The majority of these cases occurred within 8 days after the vaccination (44 cases), afterwards only single cases were recorded. 33 patients were males, 24 females (2 cases sex unknown). The majority of the patients had the postvaccinal convulsions between 7 to 36 months of age, a characteristic period for febrile convulsions. 28 patients showed a course typical for febrile convulsions. In some cases intercurrent infections (pneumonia, otitis media purulenta) could also explain the nerval reactions. In 11 cases encephalopathy or encephalitis (1 case due to mumps) had been diagnoses. 8 patients suffered later from a convulsive disorder. Between 1964 and 1974 165,000 children born in Hamburg, were immunised thrice with OPV. In this period 19 convulsions and 3 permanent convulsive disorders were observed (1 case per 8,600 vaccinees; 1 convulsive disorder per 55,000 vaccinees).

The polio neutralisation test was performed in 199 paired sera from mothers and their newborn infants from the Hamburg area and in 69 paired sera from Bamako (Mali). Antibodies against all 3 poliovirus types were demonstrated in 52.3% of Hamburg and in 78.0% of bamako mothers. The significantly inferior protection of Hamburg mothers was caused by a lower rate of polio 3 antibodies. Only 65.3% of the Hamburg mothers had polio 3 antibodies in contrast to 88.0% of Malian mothers. Newborn infants from Hamburg had significantly higher polio 2 antibody titres than their mothers, newborn infants from Bamako in contrast had significantly lower polio 2 and 3 antibody titres than their mothers. Both groups share an insufficient transferral of polio 3 antibodies. When only titres outside the range of error of the neutralisation test (1 titre step) are considered as different, all 3 polio types in both groups show agreement of titres in mother and child in more than 90%.

Among 48 adults without a history of tetanus immunization, we found with the aid of indirect hemagglutination test 20 individuals with protective tetanus antibody titers, 23 with low levels of antitoxin (under 0,1 I.U./ml) and 5 devoid of tetanus antitoxin. In two blood samples of 99 unvaccinated children under 3 years of age (taken at 7 months intervall) 12,1% showed tetanus antitoxin in the first serum sample and 16,2% in the second sample. Protective antibody titers could be found only in 4 children in each of the first and second serum sample. The data suggest a silent oral immunization by tetanus bacilli thus boosting under unhygienic conditions the tetanus immunity with advancing age.

The prevalence of antibodies to viruses associated with respiratory illnesses (influenza, corona, R.S., adeno, parainfluenza Mycoplasma pneumoniae) has been investigated in 119 children under 3 years of age (Koulikoro region Mali) and 50 persons 15-19 years of age (Bamako/Mali). In the surveillance period (March 1982-September 1982) an outbreak of respiratory disease in association with RS virus took place. A rise of CF titer has been found in 90.8% of the children; 59.1% of them presented a fourfold or greater increase of titer. The GMT values rose from 1:7 to 1:48. Concerning influenza viruses a higher incidence of positive reactions has been observed only for H3N2 viruses. A fourfold CF rise of titer has been observed for adenovirus and mycoplasma pneumoniae in 3 cases each, for parainfluenza type I and III in 2 cases each, and for parainfluenza II in 1 case. In persons 15-19 years of age the incidence of positive CF reactions was relatively high (68%-98%), but the GMT values were moderate (1:12-1:25). These data confirm that the frequency of viral respiratory diseases is the same in tropical countries as in countries with a temperate climate.

From 1950 to 1970 in Hamburg, 9240 patients under 15 years of age were treated as inpatients for pertussis. 1674 patients had pneumonia due to pertussis, 114 had pertussis encephalopathies, and 41 seizures. The fatality from pneumonia went from 2,26% (1950-1960) to 0,4% (1961-1970). Fatality from encephalopathy was less influenced (24% respectively, 17,9%). The mild clinical course of pertussis is also reflected in the reduced number of hospitalizations due to pertussis (1956, 3,7%; 1970, 0,8%). Permanent damage from complications due to pertussis was seen in 0,7% of survivors from pertussis pneumonia and in 3,4% after pertussis encephalopathy.

During a serological surveillance programme between October 1974 and September 1975 in Hamburg, 1624 sera from all age groups of the population were examined for the presence of coronavirus antibodies (OC 43 agent). 61,51% of the sera showed HI-titres between 1:8 and 1:128. The geometric mean antiboty titre (GMT) for the whole group was 1:12,2. The serological seasonal pattern suggests that coronaviruses are circulating the whole year in the urban population with a prevalence in the cold and a decrease in the warm season (June). The highest incidence of seropositive reactions (82,9%) was found in the 15-24 years old individuals (GMT 1:13,8). These data indicate an increased spread of coronaviruses in this segment of the population and a marked susceptibility of the group.

Conventional vaccinia strains were cultured at different temperatures, because it is known that vaccinia viruses which are human pathogens grow even at higher temperatures (41 degrees C). Neither the vaccination strains nor the vaccinia viruses which were isolated from vaccination vesicles after normal (n equals 7) or abnormal primary vaccinations (n equals 2) multiplied at higher incubation temperatures; Vaccinia viruses isolated from CSF of four patients with neurological complications behaved differently. Uninhibited growth at 41 degrees C (with high infection titres) suggest that the viruses isolated from CSF were vaccinia variants with abnormal characteristics. Accordingly, these variants morphologically formed plaques in Vero-cell cultures which were two to three times larger than those of vaccinia viruses obtained from CSF of primary vaccinated cases after only moderately severe general reactions, and which on temperature test responded like the viruses used in the original vaccination.

A serological survey of young nurses, mainly aged 17 to 22 years, showed that only 1.5% of nurses from pediatric departments (n = 335) were without rubella antibodies compared with 4.3% seronegative nurses from general wards (n = 278). Very rarely some nurses still considered a history of rubella as a basis of their rubella immunity. Nurses born in different parts of West Germany demonstrated various percentages of serological immunity towards rubella before the onset of their work. In Hamburg rubella vaccination has been offered already since 1972 to 15 years old schoolgirls. Therefore it was understandable, that nurses born in Hamburg (308) were seronegative, only in 2.6% whilst nurses born in other parts of Germany with later onset of the vaccination programme lacked rubella antibodies up to 8.1%.

Since the introduction of mumps vaccination in the Federal Republic of Germany 34 untoward vaccinal reactions were collected. In 2 cases of aseptic meningitis after mumps immunisation mumps virus was isolated from the CSF. The final investigation showed mumps virus (wild type) in one case; in the other a mumps vaccine-like strain (Jeryl-Lynn) was identified. Both patients recovered completely. These complications do not outweigh the enormous benefits of mumps immunisation.

The authors studied the seroconversion of 307 children, 1-11 years old, induced by Mumpsvax (136 children) and a bivalent mumps-measles vaccine (strain Jeryl Lynn/strain Moraten; 171 vaccines) by the HI-test. The seroconversion induced by the measles component of the bivalent vaccine covered 96.3% of the seronegatives prior to immunization. The comparable values for mumps antibodies were lower (Mumpsvax:80.6%; bivlant vaccine: 82.2%). An increase in titer in seropositive children was obtained in 57.1% after immunization with Mumpsvax and in 50.8% with the bivalent vaccine. Comparative studies to investigate the sensitivity of the HI-test versus the neutralisation test (NT) showed the greater accuracy of the latter. Before the vaccination with Mumpsvax, only 26.6% of 60 sera studied were found to be seronegative, whilst the NT gave a more reliable figure (55%). Similar data were found in 62 sera before immunization with the bivalent vaccine (HI-test: 33.8%; NT:66.1% seronegative). The seroconversion rates were slightly higher when the NT had been used: 75.6% (bivalent) and 81.8% (monovalent vaccine) versus 75.6% and 75%, respectively, by the HI-test.

Antibodies to cytomegalovirus (CMV) have been detected by the indirect haemagglutination test in 107 paired sera (newborn and mother) from Hamburg and 39 paired sera from Bamako (Mali). In addition, 53 unpaired sera from neonates and different mothers from Mali were evaluated for our study. In Hamburg 63,5% of both newborns and their mothers possessed CMV antibodies. The GMT values of the neonatal CMV-antibody-titres was higher than in the maternal blood (1:780 versus 1:510). In Bamako the frequency of positive reactions was evidently higher: 94,9% (maternal blood) and 82,2% (newborn cord blood). The GMT value of CMV neonates antibodies was under the level registered in their mothers sera: 1:290 and 1:450 respectively. The different socioeconomic conditions of the two groups of population studied may explain the results obtained.

Two vaccinia viruses isolated from patients with vaccinial complications (vaccinial ulcer, postvaccinial seizures) showed qualitative differences from the original parental strain. After intradermal injection of the viruses into the rabbit marked necroses developed, which the original strains did not produce. While the parental virus did not grow on the chorioallantoic membrane at 41 degrees C after 2 days incubation, the vaccinia variant produced typical lesions at that temperature. Also the yield of infectious virus on various cell systems was 1--2.5 logs higher for the virus than for the original vaccine strain. With the plaque technique differences were seen in the appearance and size of plaques between the variant and the parental vaccinia strain. These results indicate that virus of an increased pathogenicity could be isolated from the patients and this might be causally connected with the postvaccinial complications from which they were suffering.