Immunity to diphtheria in Izmir, Turkey

In order to assess immunity to diphtheria in Izmir, Turkey, a total of 743 persons 1–70 years of age were selected with cluster sampling. The information on socio-demographic characteristics, vaccination status and diphtheria history was gathered for each participant. Diphtheria antitoxin levels were measured qualitatively by using micro-enzyme immune assay. Of studied population, 79.1% had fully protective antitoxin levels ( 0.1 IU/ml). Diphtheria protection rates showed a gradual age-related decrease, reaching minimum in the 30–44 age group, in which 40.2% of these subjects had antibody titre below the full protective level. The diphtheria antitoxin geometric mean titer was highest in the 5–9 year age group (1.05 IU/ml). Then, geometric mean titer decreased with increasing age, and reached the minimum level in the 30–44 age group (0.19 IU/ml). These results suggest that in Izmir, Turkey, full serological protection against diphtheria is only detectable in 60% of the adult population. The enhancement of diphtheria immunity by booster vaccinations in adolescents and adults should be considered in Turkey.     

Diphtheria antitoxin response to DTP vaccines used in Swedish pertussis vaccine trials, persistence and projection for timing of booster

Data from two Swedish pertussis vaccine trials with various combination vaccines were used to compare anti-diphtheria antitoxin concentrations over time between different vaccines, vaccine lots and vaccine schedules. The immune responses were measured with a validated ELISA method.Results are given for 1326 children, born 1992, that were recruited to the placebo (DT)-controlled Trial I which used a 2, 4, 6 month schedule. Two DTP acellular and one DTP whole cell vaccine were used. No DT boosters were given until 5 years of age.Trial II recruited children born 1993-94 and compared three DTP acellular vaccines with one DTP whole cell vaccine. Results are given for 306 children in a 2, 4, 6 month schedule and for 531 children in a 3, 5, 12 month schedule. The latter schedule gave significantly higher diphtheria antitoxin concentrations post third dose.The various DTP acellular vaccines and an inefficacious DTP whole cell vaccine gave lower antitoxin concentrations than both an efficacious DTP whole cell vaccine and the DT vaccine. The larger differences in antigen response between vaccines was reduced in the course of time. Generally, an initial rapid decline of antitoxin concentration was followed by a slower decline; the change typically occurring when the antitoxin concentration reached 0.13-0.16 EU/ml. The time needed to reach this level was between 6 and 10 months based on the initial vaccine response.A "best-fit" combined exponential regression model was used to predict the optimal timing for booster vaccinations against diphtheria.Our data support a 3, 5, 12 month schedule followed by a fourth dose 4-5 years after the third dose, depending upon the vaccine used.     

Safety and immunogenicity of hydrogen peroxide-inactivated pertussis toxoid in 18-month-old children.

The immunogenicity and adverse effects of an acellular pertussis vaccine consisting of a purified pertussis toxin inactivated with hydrogen peroxide (PTxd) was evaluated. Children aged 15 to 30 months were injected with 10 (n = 33) or 50 micrograms (n = 34) of PTxd or with diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP) (n = 34). All children had previously received three doses of DTP during infancy. Both dosages of PTxd induced higher IgG antibody (p less than 0.05 for 10 micrograms dose and p less than 0.01 for 50 micrograms dose) and pertussis antitoxin responses (p less than 0.01 for 50 micrograms dose) than DTP. The 50 micrograms dose gave slightly higher (though not significantly) antibody responses than the 10 micrograms dose of PTxd. None of the vaccines induced detectable IgM or IgA antibody responses to pertussis toxin. At 24 h, local reactions occurred in none of the children injected with 10 micrograms PTxd, 12% with 50 micrograms PTxd and 78% with DTP. Fever at 24 h occurred in 13% after 10 micrograms PTxd, in none after 50 micrograms PTxd and in 53% after DTP. Recipients of DTP, but not of PTxd, had significant increases in neutrophils and decreases in lymphocytes and haematocrit at 24 h (all p less than 0.05). None of the groups showed changes in blood glucose at 24 h. PTxd induced pertussis toxin antibody levels similar to those observed in patients convalescing from natural pertussis. This acellular pertussis vaccine deserves further evaluation for safety and immunogenicity in infants and for efficacy in preventing pertussis.     

DTP immunization status and tetanus antitoxin titers of Mexican American children ages six months through eleven years.

Data from the Mexican American portion of the Hispanic Health and Nutrition Examination Survey (HHANES), conducted in 1982-83, were analyzed for the number of diphtheria, tetanus, and pertussis (DTP) immunizations reported for Mexican American children 6 months-11 years of age and for levels of tetanus antitoxin titers in Mexican American children 4-11 years of age. In Mexican American children 6 months-11 years, 98.2 per cent had one or more DTP immunizations reported (95 per cent CI: 97.5, 98.9%); 85.1 per cent had three or more DTP immunizations reported (95 per cent CI: 83.2, 87.0%). The reported immunization coverage in Mexican American children was corroborated by the tetanus antitoxin titers which were above the minimum protective level (greater than or equal to 0.01 IU/ml) in 99.6 per cent of the 4-11 year olds. Using the American Academy of Pediatrics' (AAP) recommendations for the number of DTP immunizations, 61.1 per cent of the children 6 months-11 years of age had the age-appropriate number of immunizations (95 per cent CI: 58.5, 63.7%). AAP immunization completion rates were higher for children who: had a source of care reported (62.1 vs 44.3%; 95% CI of the difference: 7.1, 28.5); had insurance coverage (63.5 vs 56.1%; 95% CI of the difference: 2, 12.8); lived in a standard metropolitan statistical area (SMSA)-not central city as compared to SMSA-central city or not SMSA (66.6 vs 57.1%; 95% CI of the difference: 4.3, 14.7); and had 12 or more completed years of education for the head of the household (65.4 vs 58.3%; 95% CI of the difference: 1.8, 12.4).(ABSTRACT TRUNCATED AT 250 WORDS)     

Antidiphtheria immunity of the Algerian population: a seroepidemiological study

OBJECTIVE: The antidiphtheria immunity of the Algerian population is not well known. Thus, a study was carried out on 1755 blood samples, in 1998 to better assess this vaccinal status. Three epidemics occurred in Algeria, in the years 1993, 1994, 1995, and then immunization sensitizing campaigns were introduced in September 1995. MATERIAL AND METHOD: The procedure that was used was based on the immunoenzymatic method, the reagents of which were ready for use. The interpretation of our results and vaccinal policy deduction were performed according to the VIROTECH Diphtheria ELISA technique which offers five classes in antitoxin titers: I. <0.1 IU/ml basic immunization immediately. II. 0.1-1.0 IU/ml booster immunization immediately. III. 1.0-1.4 IU/ml booster vaccination 5 years later. IV. 1.5-2.0 IU/ml booster vaccination 7 years later. V. >2.0 IU/ml booster vaccination 10 years later. RESULTS: In our series, 17.03% of the samples had a titer <0.1 IU/ml considered as insufficiently protective, an immunization was therefore recommended. 59.82% had titers ranging between 0.1 and 1 IU/ml, 5.98% had titers ranging between 1 and 1.4 IU/ml, 3.36% had titers ranging between 1.5 and 2 IU/ml, and 13.79% had titers >2 IU/ml.     

Poor immunogenicity of BCG in helminth infected population is associated with increased in vitro TGF-beta production

The only vaccine available against tuberculosis (TB), BCG, so effective in experimental animal models, has been under scrutiny for a long time owing to its variable efficacy against pulmonary tuberculosis in adults. In this study, we evaluated whether anti-helminthic therapy prior to BCG vaccination could increase the immunogenicity of BCG vaccination in helminth infected population. We recruited volunteers with evidence of prior mycobacterial infection and who were asymptomatic carriers of helminths. The subjects were randomized to receive either anti-helminthic drugs or placebo. Three months later, BCG vaccination was administered to volunteers. Mycobacterial antigen-specific cytokine responses were assessed 2 months after vaccination. The results show that peripheral blood mononuclear cells obtained from the placebo group were found to have a lower frequency of IFN-gamma (129 vs 191, p=0.03) and IL-12 (149 vs 243, p=0.013) producing cells per 2 x 10(5) PBMC (peripheral blood mononuclear cells) when stimulated in vitro with a mycobacterial antigen mixture (purified protein derivative (PPD)) compared to those from the dewormed group. On the other hand the placebo group had higher frequency of TGF-beta producing cells in response to PPD (152 vs 81.3, p=0.002) or the T cell mitogen concanavalin A (Con A) (210 vs 157, p=0.03). However, no detectable IL-4 or IL-5 producing cells were observed when cells were stimulated with PPD. Comparable numbers of both cytokine producing cells were induced in both groups upon stimulation with concanavalin A (IL-4 217 vs 191, p=0.08) and IL-5 (131 vs 103, p=0.14). The data presented here demonstrate that chronic worm infection reduces the immunogenicity of BCG in humans and this was associated with increased TGF-beta production but not with enhanced Th2 immune response.     

Immunity against diphtheria among children and adults in Izmir, Turkey

The aim of this study was to evaluate diphtheria immunity in a sample of the Turkish population having high childhood immunization coverage, including a booster dose of diphtheria toxoid at 12-15 years of age. A total of 599 persons aged 1-70 years were selected with cluster sampling. The information on socio-demographic characteristics, vaccination status and diphtheria history was gathered for each participant. Diphtheria antitoxin levels were measured qualitatively by using micro-enzyme immune assay. Of studied population, 72.3% had fully protective antitoxin levels (≥0.1 IU/ml). The rate of protection was 92.5% in the children aged 0-2 years, 93.2% in the primary school children aged 7-9 years, and 86.0% in the adolescents aged 15-19 years. After 20 years of age, diphtheria protection rates showed a significant age-related decrease, reaching minimum in the 30-39 age group, in which 47.3% of these subjects had fully protective antitoxin levels. The diphtheria antitoxin geometric mean titer (GMT) was highest in the 0-2 year age group (1.18 IU/ml). In the adolescents aged 15-19 years, diphtheria antitoxin GMT was 0.71 IU/ml. Then, geometric mean titer decreased with increasing age, and reached the minimum level in the 40-59 years age group (0.18 IU/ml). The protection rate among females was significantly lower than males (67.1% vs. 80.9%). The difference was apparent in the 20-29 and the 30-39 years age group: 80% of the males and 46.2% of the females in the 20-29 years age group, and 60% of males and 44.1% of females in the 30-39 years age group were fully protected against diphtheria (p < 0.0001). These results suggest that in Izmir, Turkey, full serological protection against diphtheria is only detectable in <50% of the young adult population, even though childhood immunization coverage is relatively high. Potentially, there is still risk of diphtheria outbreaks among the adults in our country. Therefore, a revaccination of adults with reduced doses of diphtheria toxoid should be considered to sustain diphtheria immunity.     

嘉兴市健康人群百日咳、白喉、破伤风抗体水平监测

目的了解嘉兴市健康人群百日咳、白喉、破伤风抗体水平状况。方法采用分层随机抽样方法，抽取4个年龄组健康人群220名，用试管凝集试验检测百日咳凝集抗体，用间接血凝试验检测白喉、破伤风抗毒素。结果百日咳抗体保护率为91．10％，GMT 1：887．13；白喉抗毒素保护率为97．60％，GMT 0．4283 U／ml；破伤风抗毒素保护率为95．70％，GMT 0．3097 U／ml。结论嘉兴市健康人群对百日咳、白喉、破伤风已形成了良好的免疫屏障。     

2008年费县部分健康人群百日咳、白喉、破伤风抗体水平调查

[目的]了解费县健康人群百日咳、白喉、破伤风抗体水平,评价百白破三联制剂免疫效果,为制定免疫策略提供科学依据。[方法]2008年随机抽取费县446名健康人群进行血清百日咳、白喉、破伤风抗体水平检测。[结果]检测446人,百日咳抗体保护率为68．39％,抗体几何平均滴度为1：306．56;白喉抗毒索均值为0．11IU／ml,保护率为77．13％;破伤风抗毒素均值为0．12IU／ml,保护率为76．01％。百日咳、白喉、破伤风抗体保护率,〈15岁组分别为76．53％、84．24％、83．42％。[结论]费县15岁以下健康人群对百日咳、白喉、破伤风均有较高的免疫水平,但15岁以上人群的抗体水平明显降低。     

Evaluation of diphtheria convalescent patients to serve as donors for the production of anti-diphtheria immunoglobulin preparations

AIMS: The study was conducted to evaluate the possibility of selecting convalescent diphtheria patients to serve in emergency situations as donors for the production of anti-diphtheria immunoglobulin. To select suitable donors, the criterion of an antitoxin titer >/=3.0 IU/ml was used. In addition, the effects of treatment and the effect of immunization with diphtheria toxoid on the level of anti-diphtheria toxin antibodies were evaluated. SCOPE: Three groups of diphtheria patients were included in the study. The first group (n = 23) consisted of patients who had a basic antibiotic treatment, with or without serotherapy using horse antitoxin and/or human immunoglobulin. The second group (n = 12) comprised patients examined immediately after the onset of disease. The immunological history of this group was not known. The third group (n = 20) included patients with a known immunization history, treated only with antibiotics but having received a booster immunization with diphtheria toxoid. Antitoxin titers were measured using the toxin binding inhibition (ToBI) assay. CONCLUSIONS: In the first group, 47.8% (11/23) of the patients had a diphtheria antibody titer >/=3.0 IU/ml. For most of them, however, the antibody titers could have resulted from treatment with exogenous antibodies from horse antitoxin or human immunoglobulin (18/23). Only two of the 11 high-titer subjects had received antibiotics only. Among the second group, only two (16.76%) of the patients had an antibody titer of >/=3.0 IU/ml. In the third group 50% (10/20) of the patients showed an antibody titer of >/=3.0 IU/ml prior to vaccination, and therefore could be directly considered as donors. Three weeks after booster vaccination, 70% (14/20) had an antibody titer of >/=3.0 IU/ml and 1 year after booster vaccination, 28.6% (2/7) of the subjects still had titers of >/=3.0 IU/ml. In 40% of these patients, a decrease was observed 3-4 weeks after the booster dose. It was concluded that convalescent diphtheria patients could be considered as donors in an emergency situation, since approximately half of them showed antitoxin titers of >/=3.0 IU/ml.     

Utility of dual skin tests to evaluate tuberculin skin test reactions of 10 to 14 mm in healthcare workers.

OBJECTIVE: To define the utility of 10- to 14-mm reactions to a Mycobacterium tuberculosis purified protein derivative (PPD) skin test for healthcare workers (HCWs). DESIGN: Blinded dual skin testing, using PPD and M. avium sensitin, of HCWs at a single medical center who had a 10- to 14-mm reaction to PPD when tested by personnel from the Occupational Health Department as part of routine annual screening. SETTING: A single tertiary-care academic medical center. PARTICIPANTS: Employees of the medical center who underwent routine annual PPD screening and were identified by the Occupational Health Department as having a reaction of 10 to 14 mm to PPD. RESULTS: Nineteen employees were identified as candidates and 11 underwent dual skin testing. Only 4 (36%) had repeat results for PPD in the 10- to 14-mm range, whether read by Occupational Health Department personnel or study investigators. For only 5 (45%) of the subjects did the Occupational Health Department personnel and study investigators concur (+/- 3 mm) on the size of the PPD reaction. Two of the 4 subjects with reactions of 10 to 14 mm as measured by the study investigators were M. avium sensitin dominant, 1 was PPD dominant, and 1 was nondominant. CONCLUSION: A reaction of 10 to 14 mm to PPD should not be used as an indication for the treatment of latent tuberculosis (TB) infection in healthy HCWs born in the United States with no known exposure to TB.     

Underestimation of Mycobacterium tuberculosis infection in HIV-infected subjects using reactivity to tuberculin and anergy panel

BACKGROUND: This study aimed to evaluate purified protein derivative (PPD) reactivity and its interrelationship with anergy panel and CD4+ lymphocytes in HIV-infected subjects as compared to PPD reactivity in HIV-uninfected individuals in a tuberculosis endemic and high Bacillus Calmette-Guérin (BCG) coverage environment. METHODS: Clients of four Mexico City HIV detection centres were screened for HIV-1 antibodies (ELISA or haemagglutination, Western Blot); reactivity to PPD (Mantoux PPD, 5TU RT-23), Candida (1:1000, 0.1 ml), and tetanus toxoid (10Lf, 0.1 ml); and CD4+ T cells. Active tuberculosis was excluded. Informed consent was obtained. RESULTS: From 5130 clients 1168 subjects were enrolled; of these 801 (68.6%) were HIV positive. Reactivity to PPD among HIV-positive subjects was found in 174 (22%), 261 (32.6%), and 296 (37%), at PPD cutoff levels of > or =10 mm, > or =5 mm, and > or =2 mm as compared to 224 (61%) of 367 HIV-negative individuals' reactors to PPD (> or =10 mm) (P < 0.001). After exclusion of anergic individuals using two cutoff levels for cutaneous allergens (< or =2 mm and < or =5 mm), PPD reactivity between HIV-infected and uninfected individuals continued to be significantly different. Only HIV-infected individuals with CD4+ T cells > or =500 cells/mm3 had similar reactivity to PPD as HIV-uninfected individuals. Variables associated with PPD reactivity were CD4+ T cell counts, BCG scar, HIV infection and age. CONCLUSIONS: PPD reactivity was useful to diagnose tuberculosis infection only among HIV-infected individuals with CD4+ counts > or =500 cells/mm3. Among individuals with lower counts, lowering cutoff levels or using anergy panel did not permit comparable reactivity as that observed among HIV-uninfected individuals.     

Jejunal flora of patients with megaoesophagus secondary to Chagas disease

The jejunal flora of 15 patients with megaoesophagus secondary to Chagas disease was studied and compared with that of 15 control individuals. In addition to the serological reactions for Chagas disease (immunofluorescence and complement fixation reaction), all subjects were submitted to endoscopy and X-ray of the oesophagus, gastric secretory study and investigation of the jejunal flora. The mean bacterial counts (log10) of Chagas disease patients (4.14 +/- 2.15 c.f.u./ml) was significantly higher than those of the control group (2.83 +/- 1.34 c.f.u./ml). Aerobic bacteria were isolated from 14 Chagasic patients (maximum count 10(10) c.f.u./ml) and 7 controls (maximum count 10(5) c.f.u./ml). Anaerobes were isolated from 7 patients (maximum count 10(7) c.f.u./ml) and 1 control (10 c.f.u./ml). Controls and Chagas disease patients differed significantly in the maximum acid output, but there was no statistically significant relation between bacterial counts and maximum output.     

Attenuated immune response to tetanus toxoid in young healthy men protected against tetanus

Tetanus booster is a routine procedure of tetanus prevention in populations with high risk of injury, independent of the levels of protection. But the immune response in already protected individuals is not well studied. We describe the kinetics of booster response in individuals by measuring tetanus antitoxin levels by indirect ELISA. A 6-month follow up was performed on 60 boosted individuals tested before, 1 week, 1, 2, 3 and 6 months after the booster. High initial protection (mean titer 1.08 IU/ml) and less than 3-fold increase after 1 month were observed. After 1 month of stable antitoxin levels, the levels slowly decreased and reached a mean titer of 1.78 IU/ml after 6 months. Individuals with initial levels <1 IU/ml had booster response after the first month twice as high compared to those with initial level >or=1 IU/ml. However, in both groups, the decline from 1 to 6 months was about 2-fold. Individuals already protected against tetanus exhibited an attenuated, short-lasting booster response to tetanus toxoid. This was more pronounced in individuals with pre-booster levels >or=1 IU/ml, who did not improve immune protection after the booster.     

A comparison of three vaccines against respiratory syncytial virus in calves

An inactivated vaccine against respiratory syncytial virus (RSV) was compared with two live vaccines. The inactivated (GC) vaccine consisted of glutaraldehyde-fixed bovine nasal mucosa cells persistently infected with RSV and emulsified with oil adjuvant. The live vaccines were a modified virus (MV) derived from a bovine strain of RSV and a temperature-sensitive mutant (ts-1) derived from a human strain. The GC vaccine was inoculated subcutaneously into 12 calves and the live vaccines intramuscularly into eight calves each. Nine unvaccinated calves acted as controls. The vaccines were administered in two doses 3 weeks apart and all calves were challenged intranasally with 2 X 10(7) p.f.u. of bovine RSV 3 weeks after the second dose. At the time of challenge calves given GC, MV and ts-1 vaccines had mean serum neutralizing antibody titres of 25, 19 and 2 respectively; mean titres of IgG1 antibody by radioimmunoassay were log10 4.5, 1.3 and 2.6 respectively and mean zone areas by single radial haemolysis (SRH) were 107, 27 and 36 mm2 respectively. Eleven of 12 calves given GC vaccine were completely protected against challenge but all control animals and those given the two live vaccines were infected. The mean peak titre of virus in nasal swabs of control calves was 3.0 log10 p.f.u./ml and the mean duration of virus shedding was 6.8 days. Both these parameters were significantly reduced in animals given MV and ts-1 vaccines: mean peak titres were 2.1 and 2.4 log10 p.f.u./ml and mean duration of shedding was 3.4 and 3.3 days respectively. Thus, protection correlated better with RSV antibody detected by radioimmunoassay and SRH than with neutralizing antibody. These results are discussed in relation to the possible mechanism by which protection was mediated.     

A comparison of three vaccines against respiratory syncytial virus in calves.

An inactivated vaccine against respiratory syncytial virus (RSV) was compared with two live vaccines. The inactivated (GC) vaccine consisted of glutaraldehyde-fixed bovine nasal mucosa cells persistently infected with RSV and emulsified with oil adjuvant. The live vaccines were a modified virus (MV) derived from a bovine strain of RSV and a temperature-sensitive mutant (ts-1) derived from a human strain. The GC vaccine was inoculated subcutaneously into 12 calves and the live vaccines intramuscularly into eight calves each. Nine unvaccinated calves acted as controls. The vaccines were administered in two doses 3 weeks apart and all calves were challenged intranasally with 2 X 10(7) p.f.u. of bovine RSV 3 weeks after the second dose. At the time of challenge calves given GC, MV and ts-1 vaccines had mean serum neutralizing antibody titres of 25, 19 and 2 respectively; mean titres of IgG1 antibody by radioimmunoassay were log10 4.5, 1.3 and 2.6 respectively and mean zone areas by single radial haemolysis (SRH) were 107, 27 and 36 mm2 respectively. Eleven of 12 calves given GC vaccine were completely protected against challenge but all control animals and those given the two live vaccines were infected. The mean peak titre of virus in nasal swabs of control calves was 3.0 log10 p.f.u./ml and the mean duration of virus shedding was 6.8 days. Both these parameters were significantly reduced in animals given MV and ts-1 vaccines: mean peak titres were 2.1 and 2.4 log10 p.f.u./ml and mean duration of shedding was 3.4 and 3.3 days respectively. Thus, protection correlated better with RSV antibody detected by radioimmunoassay and SRH than with neutralizing antibody. These results are discussed in relation to the possible mechanism by which protection was mediated.     

Circulating diphtheria antitoxin levels in children aged 11-14 years in relation to the vaccinal history

Diphtheria antitoxin level in serum samples obtained from 204 healthy children aged 11-14 years was determined by means of an indirect haemagglutination technique and related to the vaccinal history of the subjects. Irrespective of the time since the last toxoid inoculation, the mean antitoxin titre per ml of serum in the individuals who had received incomplete/irregular anti-diphtheria vaccination in childhood was significantly higher when the number of toxoid doses was higher (from two to more than four doses); the same was not observed for individuals given primary vaccination (three toxoid doses) according to the schedule for childhood vaccination in Italy (regular vaccinees) and one or more booster doses. Between 8 and 13 years after the last of three toxoid doses, a significantly negative association between mean antitoxin titre and time was observed only in irregularly vaccinated children (r = -0.82; p less than 0.05); nevertheless, up to thirteen years after the last vaccine dose, more than 95% of the children exhibited protective levels of antitoxin (greater than 0.125 turkey red blood cells passive haemagglutination units per ml). No significant decrease in mean antitoxin titre was observed between 4 and 10 years after the last of four either regularly or irregularly administered toxoid doses.     

The sequence of vaccinations and increased female mortality after high-titre measles vaccine: trials from rural Sudan and Kinshasa

OBJECTIVE: West African studies have hypothesized that increased female mortality after high-titre measles vaccine (HTMV) was due to subsequent diphtheria-tetanus-pertussis (DTP) and inactivated polio vaccine (IPV) vaccinations. We tested two deductions from this hypothesis in HTMV studies from rural Sudan and Kinshasa; first, there should be no excess female mortality for HTMV recipients when DTP was not given after HTMV and second, excess female mortality should only be found among those children who received DTP after HTMV. STUDIES: The Sudanese trial randomised 510 children to Edmonston-Zagreb (EZ) HTMV, Connaught HTMV or a control vaccine (meningococcal). Both the Connaught HTMV and the control group received standard measles vaccine at 9 months. In the Kinshasa study 1023 children received one dose of HTMV at 6 months or two doses at 312 and 912 months of age. FINDINGS: First, the Sudan trial is one of the few randomised studies of measles vaccine; the EZ HTMV group had lower mortality between 5 and 9 months of age than controls, the mortality ratio (MR) being 0.00 (p = 0.030). This effect was not due to prevention of measles infection. Second, both studies provided evidence that HTMV per se was associated with low mortality. In a combined analysis comparing both HTMV groups with controls, the HTMV groups had a MR of 0.09 (0.01-0.71) between 5 and 9 months of age. In Kinshasa, the HTMV recipients who did not receive simultaneous DTP had an annual mortality rate of only 1.0% between 6 months and 3 years of age. Third, the female-male MR was related to subsequent DTP vaccinations. In Kinshasa, the female-male MR was only 0.40 (0.13-1.27) among the HTMV recipients who did not receive further doses of DTP. In Sudan, the female-male mortality ratio in the EZ group was 3.89 (95% CI 1.02-14.83) and the female-male MR increased with number of doses of DTP likely to have been given during follow-up (trend, p = 0.043). Fourth, in Kinshasa, mortality was higher among children who had received HTMV and DTP simultaneously than among children who had received HTMV alone (MR = 5.38 (1.37-21.2)). CONCLUSIONS: Measles vaccine is associated with non-specific beneficial effects. When not given with DTP, HTMV per se was associated with low mortality. Increased female mortality was not found among children who did not receive DTP after HTMV. Hence, our deductions were supported and the sequence or combination of vaccinations may have an effect on sex-specific mortality patterns in low-income countries.     

Mass chemoprophylaxis of lymphatic filariasis with a single dose of ivermectin in a Polynesian community with a high Wuchereria bancrofti infection rate.

In April 1991 supervised mass prophylaxis of lymphatic filariasis with a single dose of ivermectin, 100 micrograms/kg, was carried out in a Polynesian village with a high infection rate of Wuchereria bancrofti in humans and active transmission by the vector mosquito, Aedes polynesiensis. Of 876 inhabitants aged 3 years or more (pregnant women excluded), 864 (98.6%) were treated. Simultaneously, venous blood samples were collected from 577 (97.5%) of the 595 inhabitants aged 15 years or more, of whom 122 (21.4%) were found to be microfilaria (mf) carriers (86 males and 36 females). The geometric mean microfilariae (GMM) count was 358.7 mf/ml for the whole group, 387 mf/ml for males (range 1-8160 mf/ml) and 280 mf/ml for females (range 1-7769 mf/ml). Following treatment, 33 (3.8%) of the 864 persons treated experienced some adverse reactions (21 with grade 1 and 12 with grade 2). Of the 33 with reactions, 29 were among the 122 (23.8%) mf carriers and 4 among the 831 (0.5%) non-microfilaraemic persons. Six months later, 123 (21.1%) of 584 inhabitants sampled were microfilaraemic: the GMM count for the whole group was 106 mf/ml (1-8177), with 29 mf/ml (1-3740) in 35 female and 177 mf/ml (1-8177) in 88 male carriers. Of these 123, 15 (whose GMM count was 4.5 mf/ml; range 1-204) were amicrofilaraemic 6 months before, and 19 had a microfilaraemia level higher than that 6 months earlier, before treatment. 117 of the 122 carriers identified in April were resampled: comparison of their GMM counts before and 6 months after mass treatment indicated that treatment with a single dose of 100 micrograms/kg ivermectin resulted in a reduction of microfilaraemia by 69%.     

Delayed hypersensitivity. A critical evaluation of five recall antigens in a large reference population

The reactivity to five recall antigens, candida, mumps, PPD, varidase and trichophyton and the corresponding diluents was tested in 840 healthy persons aged between 17 and 101 years. Candida antigen was tested in a lower (l) and a higher (h) dose. The size of reactions did not follow a Gaussian distribution and we therefore used the 10th and 5th percentiles instead of standard deviation to define the limits between positive, weak and negative reactions. The number of positive reactions to each of candida-h, mumps, PPD and varidase was between 80 and 95 per cent in patients less than 60 years of age and above this age it varied between 0 and 85 per cent. The number of positive reactions to candida-l and trichophytin was low in all ages. The reactivity was regarded as normal if there was a positive reaction i.e.sum of right angle diameters >10 mm to atl east one antigen, relatively anergic if there was only a weak reaction (7-9 mm) and anergic if there was a negative reaction (0-6 mm) to all antigens. A normal reaction was found in 100 per cent of subjects up to 60 years of age, and in 95 per cent up to 30 years. Among those with normal reactivity, positive results were found with candida-h alone in between 67-93 per cent, candida-h + mumps between 92-100 per cent and candida + mumps + PPD in 100 per cent irrespective of age.