Transmission of mumps virus from mumps-vaccinated individuals to close contacts

During a recent mumps epidemic in the Netherlands caused by a genotype D mumps virus strain, we investigated the potential of vaccinated people to spread mumps disease to close contacts. We compared mumps viral titers of oral fluid specimens obtained by quantitative PCR from vaccinated (n = 60) and unvaccinated (n = 111) mumps patients. We also investigated the occurrence of mumps infection among the household contacts of vaccinated mumps patients. We found that viral titers are higher for unvaccinated patients than for vaccinated patients during the 1st 3 days after onset of disease. While no symptomatic cases were reported among the household contacts (n = 164) of vaccinated mumps patients (n = 36), there were cases with serological evidence of asymptomatic infection among vaccinated household contacts (9 of 66 vaccinated siblings). For two of these siblings, the vaccinated index patient was the most probable source of infection. We conclude that, in this particular outbreak, the risk of a close contact becoming infected by vaccinated patients was small, but present.     

Studies on the reactogenicity and immunogenicity of the BRD-2 and RA27/3 live attenuated rubella vaccines

A study to compare the reactogenicity and immunogenicity of the BRD-2 and RA27/3 rubella vaccine strains was conducted in GuangXi, China in 1982. Ninety eight susceptible children between two and six years of age, with haemagglutination inhibition (HI) antibody titres of <10, were inoculated with RA27/3 vaccine strain. A similar group of 103 children were inoculated with BRD-2 vaccine strain; 110 uninoculated children served as a control group. The percentages of children who had fever reactions were 30.09% for RA27/3, 20.04% for BRD-2, and 24.50% for the uninoculated group. Neither vaccine evoked a high fever reaction. For both vaccines, the seroconversion rates estimated 42 days after immunization were 100%. The geometric mean titre of HI antibody was 144.4 ± 2.04 for recipients of RA27/3, and 116.1 ± 2.0 for those vaccinated with BRD-2. The rate of excretion of virus from the nose and throat was 26.67% for the recipients of RA27/3 and 23.08% for those who received BRD-2. No vaccine virus was isolated from the uninoculated susceptibles who were in close contact with the vaccinated children. Furthermore, the latter group remained seronegative when tested after 42 days of contact with the vaccinated. Hence, it appears that both RA27/3 and BRD-2 vaccine viruses have no capacity for being transmitted to unvaccinated contacts. In susceptible adolescents immunized with the BRD-2 vaccine viruses have no capacity for being transmitted to unvaccinated contacts. In susceptible adolescents immunized with the BRD-2 vaccine strain, a mild febrile reaction was observed. Rash and arthritis reactions were not found. The seroconversion rate was 100%, and the geometric mean titre of antibody was 65.63 ± 1.69. These results indicated that the BRD-2 strain selected and prepared by the National Vaccine and Serum Institute in Beijing, China is an attenuated virus strain with mild reactogenicity and good immunogenicity.     

Fatal respiratory diphtheria in a U.S. traveler to Haiti--Pennsylvania, 2003

Respiratory diphtheria can be severe or fatal in unvaccinated persons; even with appropriate treatment, 5%-10% of patients with diphtheria die. For >50 years, vaccination against diphtheria has been recommended for children and adults in the United States. Persons who are unvaccinated or vaccinated inadequately can contract diphtheria during travel to areas where the disease is endemic, putting them and their close contacts at risk for severe illness. This report describes fatal respiratory diphtheria in an unvaccinated Pennsylvania resident who had visited Haiti, a country where the disease is endemic. The case highlights the need for all international travelers to be up-to-date with all recommended vaccinations, including a primary series of diphtheria toxoid-containing vaccine.     

The effectiveness of BCG vaccination of the newborn against childhood tuberculosis in Bangkok

The Central Chest Clinic, Bangkok, Thailand, undertook a study among child contacts of newly discovered sputum-smear-positive patients with pulmonary tuberculosis to determine the effectiveness of BCG vaccination in young children. The study design resembled that of a controlled trial except that it was retrospective for vaccination, i.e., the vaccinated and control groups were not randomly selected. For this reason a number of measures were taken to allow for the comparability of groups to be verified and for adjustments to be made if necessary. The study was initiated in September 1981 and terminated in June 1984, after 971 index cases who reported contact with young children had been registered. Registration and initial examinations were completed for 1506 child contacts. The field teams could not trace 124 reported child contacts. In the case of 8 children, the initial examination was refused. Within a week of the detection of the index case, a visit was made to the household and personal data were collected. The contact children then were offered a clinical and X-ray examination at the Central Chest Clinic for the examinations. A clinical record was prepared for each child contact, the site of BCG vaccination was covered with a dressing (even if there had been no vaccination or scar), and the pediatrician administered a clinical examination and made a full-plate postero-anterior X-ray. The X-ray picture was examined by 2 readers. Suspect children were followed up for as long as there were medical indications. When indicated by the clinical or X-ray examination, a laryngeal swab was taken for culture and gland biopsies were made and examined by histopathology and culture. If tuberculosis was strongly suspected, treatment was initiated at once with rifampicin and isoniazid. For each child a final diagnosis was made at the end of the study. A scoring system proposed by WHO was used to obtain an indication of the probability of tuberculosis. As many as 1218 (81%) of the children had a BCG scar, and among those without a scar, 35 had a record of vaccination. Vaccination coverage as well as disease risk appeared to be associated with age. Stratification by age showed that this did not affect the calculated effectiveness of BCG vaccination. Apart from age, no differences between the vaccinated and the unvaccinated children were observed that call for stratification of the material. 284 tuberculosis suspects were found, 218 among the 1253 vaccinated and 66 among the 253 unvaccinated participants. The total incidence of tuberculosis was 14.5%; it was 12.6% among the vaccinated and 23.6% among the unvaccinated. Based on the data presented in Tables 1 and 8, and adjusting for the estimated 55 vaccinated children included among those without a scar or a vaccination record, the observed efficacy is 53% with 95% confidence limits of 64% and 38%; the observed number of cases among the vaccinated is 185 less than expected. Thus, although efficacy appears less, the effectiveness is far higher than with a more stringent diagnostic criteria.     

SARS-CoV-2 infection risk among vaccinated and unvaccinated household members during the Alpha variant surge – Denver,Colorado, and San Diego,California, January–April 2021

BackgroundCOVID-19 vaccination reduces SARS-CoV-2 infection and transmission. However, evidence is emerging on the degree of protection across variants and in high-transmission settings. To better understand the protection afforded by vaccination specifically in a high-transmission setting, we examined household transmission of SARS-CoV-2 during a period of high community incidence with predominant SARS-CoV-2 B.1.1.7 (Alpha) variant, among vaccinated and unvaccinated contacts.MethodsWe conducted a household transmission investigation in San Diego County, California, and Denver, Colorado, during January-April 2021. Households were enrolled if they had at least one person with documented SARS-CoV-2 infection. We collected nasopharyngeal swabs, blood, demographic information, and vaccination history from all consenting household members. We compared infection risks (IRs), RT-PCR cycle threshold values, SARS-CoV-2 culture results, and antibody statuses among vaccinated and unvaccinated household contacts.ResultsWe enrolled 493 individuals from 138 households. The SARS-CoV-2 variant was identified from 121/138 households (88%). The most common variants were Alpha (75/121, 62%) and Epsilon (19/121, 16%). There were no households with discordant lineages among household members. One fully vaccinated secondary case was symptomatic (13%); the other 5 were asymptomatic (87%). Among unvaccinated secondary cases, 105/108 (97%) were symptomatic. Among 127 households with a single primary case, the IR for household contacts was 45% (146/322; 95% Confidence Interval [CI] 40–51%). The observed IR was higher in unvaccinated (130/257, 49%, 95% CI 45–57%) than fully vaccinated contacts (6/26, 23%, 95% CI 11–42%). A lower proportion of households with a fully vaccinated primary case had secondary cases (1/5, 20%) than households with an unvaccinated primary case (66/108, 62%).ConclusionsAlthough SARS-CoV-2 infections in vaccinated household contacts were reported in this high transmission setting, full vaccination protected against SARS-CoV-2 infection. These findings further support the protective effect of COVID-19 vaccination and highlight the need for ongoing vaccination among eligible persons.     

Paralytic poliomyelitis in Ontario: laboratory studies of two recent cases

Sporadic cases of paralytic poliomyelitis are being reported with increasing frequency, particularly in unvaccinated persons, in several countries in which the disease had been absent for several years following adequate initial vaccination programmes. In Ontario, two paralytic cases occurred in unvaccinated children after several disease-free years. Detailed studies of the strains of poliovirus type 1 isolated from these patients showed that they were not vaccine strains. Contact surveillance in one case showed that 21 originally unvaccinated contacts were also excreting virulent virus.     

Horizontal transmission of a human rotavirus vaccine strain--a randomized, placebo-controlled study in twins

Transmission of excreted vaccine-derived infectious virus from vaccinated to unvaccinated individuals is possible within close contacts. This randomized (1:1), double-blind study evaluated the potential for transmission of human rotavirus vaccine strain, HRV (Rotarix™) from vaccine recipients to unvaccinated close contacts (twins). 100 pairs of healthy twins aged 6-14 weeks at the time of Dose 1 of HRV vaccine/placebo were enrolled and one randomly selected twin from each pair received two vaccine doses and the other received placebo doses (at 2 and 4 months of age). Presence of vaccine strain in the stool samples of placebo recipients was an indicator of transmission. Serial stool samples were tested for rotavirus using ELISA at pre-determined time points; rotavirus positive stool samples were tested with RT-PCR and reverse hybridization assay to identify G1P[8] vaccine strain. If G1P[8] vaccine strain was detected, the complete genome was sequenced to assess the similarity between viral isolates. Immunogenicity and safety of HRV vaccine in transmission cases was assessed. 15 transmission cases were reported in 80 evaluable twins who received placebo and the transmission rate was 18.8% (95% CI: 10.9-29.0%). None of the transmission cases was associated with gastroenteritis symptoms. Anti-rotavirus IgA seroconversion was 62.5% (95% CI: 51.0-73.1%) (HRV) and 21.3% (95% CI: 12.9-31.8%) (placebo) 7-weeks post-Dose 2; seroconversion in transmission cases was 26.7% (95% CI: 7.8-55.1%). Genetic variations or amino acid substitutions in transmission cases were similar to that seen in corresponding vaccine recipients. Transmission of HRV vaccine strain to unvaccinated twins living in close contact occurred, however, they were not associated with increased of gastroenteritis. Whether transmission leads to indirect protection among unvaccinated individuals remains unknown at this stage.     

Results of a study on the under-detection of meningococcus in vaccinated subjects in Galicia

BACKGROUND: On the basis of active surveillance and the monitoring of Meningococcal Disease (MD) following the vaccination campaign carried out in Galicia, it was observed that the proportion of isolations of the serogroups responsible for the disease among individuals suspected of Meningococcal Disease (SMD) who had been vaccinated was lower than among unvaccinated individuals. In view of this situation, a study was made in order to determine whether in the origin of those SMDs that were not isolated, we would find N. Meningitidis serogroup C, and to quantify the significance of the sub-detection of same. METHODS: For this purpose, and during the period under study (from the 26th week of 1997 to the 14th week of 1999), blood and cephalorachidian fluid samples were taken from the SMDs without isolation for their study with C protein reagent for type and serogroup. The analysis of the samples was performed by the microbiology laboratory of the Clinical Hospital of Santiago de Compostela. RESULTS: Of the 120 cases notified during the period under study, 65 were analysed by C protein reagent (38 vaccinated and 27 unvaccinated), with a positive reading for N. meningitidis in 65% (42 samples) 74% in vaccinated individuals and 52% in unvaccinated. By estimating, on the basis of the cases studied, the results for the total, and excluding the C protein reagent negative cases, we find that, for serogroup C, in only 27% of the cases occurring in vaccinated individuals was it possible to isolate it, in comparison with 80% in the case of unvaccinated subjects (p < 0.0001). These percentages are, in the case of serogroup B, 59% and 71%, respectively, a difference which is not statistically significant. CONCLUSIONS: The vaccine brought about an true sub-detection of serogroup C meningococci in the vaccinated cases.     

The effectiveness of influenza vaccination among nursery school children in China during the 2016/17 influenza season

BackgroundThe effectiveness of influenza vaccine among nursery school children has not been systematically studied. We conducted a cohort study of children from 13 nursery schools in Suzhou, China, to estimate the effectiveness of influenza vaccine against laboratory-confirmed influenza during 2016–17.MethodsChildren aged 36–72 months were chosen from 13 nursery schools from 3 District in Suzhou. The surveillance started 2 weeks after vaccination during October 2016–February 2017. Class teachers reported the names of students with ILI (influenza-like illness) to study clinicians on each school day. Further, local physicians collected the student’s nasopharyngeal swab or throat swab, either at a study clinic or at the child’s home. The swabs were sent to the National Influenza Network Laboratory in Suzhou Center for Disease Control and Prevention for influenza testing by RT-PCR.ResultA total of 4614 children were enrolled, of which 15 children (vaccinated: 2; unvaccinated: 13) were lost to follow-up. Of the remaining 4599 children, 558 swabs were collected. Among these swabs, 70 samples tested positive for influenza virus; 17 in the vaccinated group (B Victoria: 2; H3N2: 15) and 53 in the unvaccinated group (B Victoria: 14; A(H1N1)pdm09: 1; H3N2: 38). The overall influenza vaccine effectiveness (VE) during the influenza season of 2016–2017 was 20.6%. The incidence of developing ILI symptoms and healthcare seeking behavior through clinical visits was significantly lower in vaccinated children than in the unvaccinated group.ConclusionInfluenza vaccine protection in vaccinated and unvaccinated children showed no statistical difference and the VE percentage varied for different virus subtypes. However, the incidence rate of developing ILI and healthcare seeking behavior was significant lower in the vaccinated group than in the unvaccinated children. Larger studies are required to estimate the VE according to the influenza type, subtype, and lineage during influenza seasons in China in the future.     

The use of vaccinia hyperimmune gamma-globulin in the prophylaxis of smallpox

This paper records an attempt to assess the prophylactic value of immune gamma-globulin, prepared from the serum of recently vaccinated adults, in the protection of close contacts of smallpox in Madras. The results serve to confirm findings of a previous study made in Madras in 1953, and show that the incidence of smallpox in close contacts given immune gamma-globulin prophylactically was about a quarter of that in the control contacts who received no such passive immunization—a statistically significant difference. Because of the limited supply of immune gamma-globulin, it is likely that its prophylactic use will be restricted to those especially at risk, for example, close unvaccinated family contacts, newborn infants and pregnant women.     

社区儿童接种b型流行性感冒嗜血杆菌结合疫苗的前瞻性队列研究

目的评价社区儿童接种b型流行性感冒嗜血杆菌[Haemophilus Influenzae(Hi)Type b,Hib]结合疫苗的免疫效果。方法采用前瞻性队列研究方法分为疫苗接种组与非疫苗接种(对照)组,用细菌培养法、巢式聚合酶链反应检测两组儿童Hi携带状况,分析Hi携带率及下呼吸道疾病罹患率。结果两组儿童Hib携带率均较低;对照组未定型Hi阳性率显著高于接种组,以2～3岁尤为明显;各年龄组中对照组儿童支气管炎罹患率均显著高于接种组,Hib结合疫苗对儿童支气管炎发病的保护效果>90%;对照组中Hi培养阳性者气管炎发病显著高于Hi培养阴性者。结论儿童支气管炎的发病与Hi携带率高有关,接种Hib疫苗后导致Hi携带率下降以及支气管炎发病减少。     

Pattern of intrafamilial transmission of smallpox in Calcutta, India

The pattern of intrafamilial transmission of smallpox in Calcutta was studied in 43 index cases, 3 of which were haemorrhagic, 14 confluent, and 26 discrete. They had 741 contacts. The attack rate in vaccinated contacts was significantly less than in unvaccinated contacts, but there was no such difference in the case rates caused by severe and mild index cases. Females had higher attack rates than males, the difference being more marked among the vaccinated. The vaccination status of the index cases seemed to affect their secondary case rates. The incidence of secondary cases among contacts living in the same room as a patient and in other rooms in the same compound was practically equal.     

Secondary analyses of the efficacy of two acellular pertussis vaccines evaluated in a Swedish phase III trial

A placebo-controlled efficacy trial of two acellular pertussis vaccines carried out in Sweden in 1986-87 used culture confirmation as the principal case definition. However, the sensitivity of pertussis culture is low, and secondary analyses using more sensitive serological diagnostic criteria have therefore been carried out. These analyses confirm that vaccination with pertussis toxoid alone does protect against typical whooping cough with laboratory confirmation, but show that it does not protect against infection or colonization. There is evidence that the addition of filamentous haemagglutinin provides some protection against infection. Bacterial isolation rates were lower in vaccinated than unvaccinated children with serologically confirmed pertussis and increased with disease severity.     

An inactivated bovine virus diarrhoea virus (BVDV) type 1 vaccine affords clinical protection against BVDV type 2

This study was designed to answer to two distinct questions. Firstly, is it possible to reproduce clinical signs of acute bovine virus diarrhoea virus (BVDV) type 2 infection including signs of haemorrhagic disease under experimental conditions in cattle at 20 weeks of age? Secondly, what is the extent of the protection afforded by vaccination with an inactivated BVDV type 1 vaccine against BVDV type 2 infection? Calves were vaccinated at 12 and 16 weeks of age with a commercially available inactivated BVDV type 1 vaccine (Bovilis BVD). At 20 weeks they were challenge infected with BVDV type 2 virus together with unvaccinated control calves. The unvaccinated animals developed typical signs of respiratory disease, diarrhoea with erosions and haemorrhages along the whole length gastro-intestinal tract, and depletion of lymphocytes in lymphatic organs. These signs were either absent or markedly less severe in the vaccinated animals. The beneficial effects of vaccination were most striking in the haematological parameters thrombocytopenia and leukopenia. It can be concluded that vaccination with Bovilis BVD affords cross-protection against clinical effects of a challenge-infection with heterologous type 2 BVDV.     

Clinical observations on smallpox: a study of 1233 patients admitted to the Infectious Diseases Hospital, Calcutta, during 1973

The paper presents clinical observations on 1 233 persons with smallpox who were admitted to the Infectious Diseases Hospital, Calcutta, in 1973. The disease was of the modified type in 53 patients (4.3%), the ordinary type in 717 (58.2%), the flat type in 249 (20.2%), and the haemorrhagic type in 214 (17.3%). The fatality of these types of smallpox was found to be 5.7%, 26.8%, 88.4%, and 98.1%, respectively, and the overall case fatality was 50.7%. The haemorrhagic type was found mainly among older patients and affected males more often than females. The vaccination status of 1 218 patients was known. Of these, 901 (73.9%) were unvaccinated and had a fatality rate of 53.4%, whereas the 317 (26.1%) vaccinated patients had a fatality rate of 36.5%. Among the 201 haemorrhagic cases, 145 patients were unvaccinated (16.09% of the total number unvaccinated) and 56 (17.67%) had been vaccinated. Of 34 patients vaccinated during the incubation period, 19 (41.1%) died, whereas of 18 patients who had been vaccinated after the onset of fever, but before the appearance of rash, 9 (50%) died.     

Levels of bactericidal antibodies against meningococcus C after vaccination in 2- to 6-year-old children in Andalusia

BACKGROUND: In 1997, 18.5% of the cases of Meningococcal Disease caused b serogroup C in Andalusia were children between 2 and 4 years of age; ages where the initial immune response and the duration of the capsular A + C meningococcal polysaccharide vaccine is less than in older age groups. Research was designed in order to measure the immune response produced by this vaccine in children from 2 to 6 years of age and to compare it with the natural immunity present in unvaccinated children. METHODS: I. Dual monitoring study: a) groups of children vaccinated previously and control groups, b) groups of children who were going to be vaccinated, for pre and post-vaccination (1, 6 and 12 months) analysis and a control group. II. The bactericidal activity was measured according to the standardised protocol of the CDC with regard to the strain of N. meningitidis C-11. The sera with bactericidal activity (TAB) > 1:8 were considered to be protective. RESULTS: 1 and 2 months following vaccination, the proportion of TAB > 1:8 was significantly higher than that of the control group (65.6% and 73% in comparison to 2.2% and 12%). In the pre-vaccine and post-vaccine (after 6, 7, 12 and 13 months) verification, no significant difference between vaccinated individuals and controls was observed. CONCLUSIONS: The differences between vaccinated and unvaccinated individuals 1 and 2 months following vaccination indicate seroconversion in the vaccinated individuals. For the age group of between 2 to 6 years of age, the bactericidal activity acquired decline quickly, as, after 6 months, differences between this group and the control group are no longer observed.     

Emergency vaccination of sheep against foot-and-mouth disease: significance and detection of subsequent sub-clinical infection

This study has quantified the level of foot-and-mouth disease virus (FMDV) replication and shedding in vaccinated sheep and correlated this to the severity of clinical signs, the induction of antibodies against FMDV non-structural proteins (NSPs) and the transmission of virus to in-contact vaccinated sentinel sheep. To mimic an emergency vaccination regime in the field, sheep were vaccinated with O(1) Manisa vaccine and 4 or 10 days later were indirectly challenged with aerosols from O(1) UKG FMDV infected pigs. Vaccinated and control unvaccinated sheep were monitored for a minimum of 39 days post-challenge. The vaccinated sheep became sub-clinically infected, with reduced virus replication and excretion compared to unvaccinated and clinically infected sheep. Seroconversion to NSP was weak and transient in sheep in which virus replication was of low level and short duration. Virus transmission from vaccinated sub-clinically infected sheep to introduced vaccinated sentinels was not sufficient to cause NSP seroconversion or significant virus shedding. 10% of 10 days and 20% of 4 days vaccinated sheep were virus carriers at greater than 28 days post-challenge compared to 37.5% in the unvaccinated and clinically infected sheep. These results suggest that the low levels of virus replication likely if an effective vaccine is administered at least 4 days prior to challenge exposure are unlikely to result in the spread of infection even under intensive management conditions. Although it may be difficult to detect this infection by serosurveillance, the significance of missing it is likely to be low and the main value of such testing will be to detect undisclosed clinical infection resulting from lack of observation or from exposure to virus before or very soon after vaccination or from vaccine failure due to maladministration or inappropriate strain selection.     

Virus excretion in smallpox. 2. Excretion in the throats of household contacts

Throat swabs of 34 of 328 family contacts of 52 smallpox cases, examined 4-8 days after the onset of the disease in the family, were positive for variola virus. The log titre of virus per swab ranged from 2 to 3.95. A higher proportion of unvaccinated than of vaccinated contacts excreted the virus. Only 4 of the virus-positive contacts developed clinical smallpox; this occurred 5-7 days after their swabs were examined. Excretion of virus in the throats of these contacts, a few of whom were in the incubation period of the disease, suggests the possibility that they could have spread the infection. This possibility, if kept in mind, may help in tracing the source of infection or in determining the incubation period in a few instances when difficulty is experienced.     

Horizontal transmission of the Leningrad-3 live attenuated mumps vaccine virus

Here we describe symptomatic transmission of the Leningrad-3 mumps vaccine virus from healthy vaccinees to previously vaccinated contacts. Throat swab and serum samples were taken from six symptomatic mumps cases and from 13 family contacts. Assessment of serum IgG and IgM anti-mumps virus antibodies and IgG avidity testing was performed using commercial test kits. Sera neutralizing antibodies were measured by plaque reduction neutralization assay using the L-3 vaccine mumps virus as the target. All six of the symptomatic mumps cases and three contact subjects tested positive for mumps by RT-PCR. The genomic sequences tested (F, SH and HN genes) of all nine of these samples were identical to the L-3 mumps vaccine strain. All 13 contacts were asymptomatic; however clear serological evidence of mumps infection was found in some of them. The likely epidemiological source of the transmitted L-3 mumps virus was children who were recently vaccinated at the schools attended by the six symptomatic mumps patients described here. The L-3 mumps vaccine virus can be shed and transmitted horizontally, even to subjects previously vaccinated with the same virus.     

Immunity to rubella before and after vaccination against measles, mumps and rubella (MMR) at 12 years of age of the first generation offered MMR vaccination in Sweden at 18 months

In 1982, a two-dose programme of vaccination against measles, mumps and rubella (MMR) at the ages of 18 months and 12 years was introduced in Sweden. In 1992–1993, the first group of children vaccinated at 18 months reached the age of 12, i.e. the time for a second dose. In connection with this 12-year vaccination, 376 children were recruited, investigated concerning earlier MMR vaccination and bled prior to and 2 months after the immunization. Two hundred and twenty of them had a documented, earlier MMR vaccination and 156 had not. The latter were classified as unvaccinated. The antibody status against rubella was measured by the haemolysis-in-gel method. Prior to the present vaccination, 3% of the earlier vaccinated group totally lacked any sign of antibodies. In the presumably unvaccinated group, this figure was 76%. After the vaccination all children showed signs of antibody acitivity and all reached the antibody level of ≥15 international units, i.e. in our tests a zone dia. of approx 8 mm. However, the secondly vaccinated children ended up with a mean antibody level of 10.7 mm which was slightly lower than the level, i.e. 11.0 mm of those lacking earlier vaccination history and prevaccination seronegative. The earlier unvaccinated but pre-immune children reached a mean level of 11.2 mm. In general, those with relatively high, pre-vaccination, antibody levels reacted less to the booster than those with low or no pre-vaccination immunity. The booster thus appeared to restore the antibody levels of the low-titre children.