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Aim. In order to assess the consequences of different clinica] approaches in the prenata] management of congenital toxoplasmosis, we retrospectively reviewed 58 pregnant women with Toxoplasma seroconversion and prospec­ tively enrolled their 59 infants, referred to us from 1999 to 2004. Metbods. Data on clinica!, laboratocy and de­ mographic characteristics of the pregnant women were collected. Their children were entered intoa 48-month follow-up progcamme in which clinica , instrumental, ophthalmo­ logic and serologic evaluations were carried out at birth, at 1, 3, 6, 9, 15, 18, 24, 36 and at 48 months of life. Paediatric treatment with Spiramycin alone or alternated with Pyrime­ thamine-Sulphadiazine was administered ac­ cording to the different clinica! cases. Resu/Js. Time of infection was dated in the tlrst trimester for 24 women (41%), in the second trimester for 18women (31%) and in the third trimester for 16 (28%). In the first trimester of pregnancy 20 of the 24 infected women had undergone amniocentesis, while the test had not been performed on any of the women in­ fected in the third trimester. Serological fol­ low-up revealed that 11(19%) of the infants had been infected. An alternating regimen with Pyrimethamine-Sulphadoxine was adminis­ tered to the infected children.Ali the infantswere clinically asymptomatic, and the instru­ mental follow-up revealed specific toxoplas­ mosis anomalies in 4/11infected children. Conclusion. Ouc results highlight issues and problems concerning current prenata! diag­ nostic tests and the therapeutic approachbased on PCR testing of amniotic fluid alone. Thein­ cidence of ocular-cerebral lesions obsecved in children born to women with seroconversion in the third trimester raises questions about the diagnostic and therapeutic approach for these women and their offspring.Paediatric ther.tpeutic protocol,with alternating Pyrime­ thamine-Sulphadiazine regimen, applied also to asymptomatic children born to women with inadequate prenata] diagnostic management, could prevent severe sequelae.

Auxological and endocrinological complications frequently occur in children with connatal HIV infection. These complications seem to be related both to the infection itself and the antiretroviral therapy. Many children consequently show height-weight and pubertal retardation without any evidence of hormonal deficit. We studied 10 children with connatal HIV infection who were enrolled in this analysis and followed up for 7 years in order to evaluate their height-weight growth, pubertal maturation, bone age progression and hormonal pattern [basal Growth hormone (GH) and GH after Clonidine or Insulin stimulation, Insulin-like Growth Factor 1 (IGF-1), Insulin-like Growth Factor Binding Protein 3 (IGFBP-3), FSH, LH, ACTH and Cortisol, TSH, fT4, T4, T3, Ab-TGO, Leptin]. Three children showed a height lower than 3rd centile during the first two years of their life and in prepubertal age, with recurring improvement in their growth rate. Weight growth was very compromised in one girl, remaining firmly lower than 3rd centile during the follow-up. Three children presented a weight lower than 3rd centile until they were two years old. However, a height growth rate higher than 10th centile was found in nine children throughout the follow-up, while it was pathological in five children. The blood level of Leptin was higher at the beginning of the study: 0.82 - 11.68 ng/l (M+/-DS: 3.29+/-4.15) than at its conclusion: 0.2 - 3 ng/l (M+/-DS: 1.65+/-1.01). There was a statistically significant correlation between leptinemia and the CD4/CD8 count (p: 0.010; r: 0.916) and the CDC classification (p: 0.006; r: 0.937), indicating a strong relationship with the degree of virological and immunological impairment. The authors stress the importance of a careful height-weight growth rate control in HIV-infected children, as it reflects the clinical and virological course of the disease. Adequate control of the infection allows physiological growth in most patients. Moreover, we emphasize the utility of IGFBP-3 and IGF-1 measurements, since they represent growth markers which are more exact and better capable of reproduction than GH.

Aim. In order to study the impact of clinical and diagnostic parameters on the clinical outcome of children with central nervous system tuberculosis (CNS-TB), we retrospectively reviewed all cases of CNS-TB diagnosed over a 32-year period at the Children's Hospital of Palermo, Italy. Methods. Data were collected with regard to the clinical, laboratory and demographic characteristics of patients, as well as the results of radiological investigations and data on clinical outcome. In relation to the date of introduction of new diagnostic methods (indirect as well direct) and to the change of treatment periods, the authors compared the clinical outcome of patients admitted prior and after 1984. They also classified the patients into 3 different stages of illness according to the severity of the disease on admission. Results. We identified 80 patients with CNS-TB. The mean age of the children was 3 years with 54% of patients younger than 5 years. The contact source was documented in 40 patients (50%). The mean duration of symptoms prior to admission was 22 days (range 5 days - 3 months). Mantoux skin test was positive on admission in 50 patients (62%). CSF smear microscopy and culture were positive in 29% and 45% of patients respectively. PCR for Mycobacterium tuberculosis introduced in 1994 was positive in 11 out of 13 tested patients. Determination of CSF γδT lymphocytes composition applied in 7 patients shows a predominance of Vγ9/Vδ2 T lymphocytes. Fifteen subjects (19%) died; 11 (13%) suffered from permanent sequelae. The died children and those with permanent sequelae were younger than the others (p

Mediterranean Spotted Fever is an acute febrile disease caused by Rickettsia conorii and transmitted to humans by the brown dog tick Rhipicephalus sanguineus. Nearly 400 cases are reported every year in Sicily, mainly from June to September. The aim of this study is to compare the clinical and laboratory features of two different groups of patients , one of adults and one of children. The analysis included all adult patients with MSF diagnosed at the Institute of Infectious Diseases, Paolo Giaccone University Polyclinic in Palermo, during the period January 2007- August 2010 and all the children diagnosed with MSF at the G. Di Cristina Children Hospital in Palermo during the period January 1997- December 2004. On admission, a complete physical and laboratory examination was carried out on every patient. An indirect immunofluorescence assay for Rickettsia conorii was performed in every case, a PCR assay was performed with blood samples from some adult patients. Analysis of the results confirms that MSF is a benign, and self-limiting disease in children, while severe complications can often arise in adults.

To define the pattern of HAV infection in Italy and to study the differences among geographic areas (northern, central and southern Italy) and age-classes, we performed HAV antibody testing on sera collected in 1996-1997 from a large sample of the Italian population and compared the results with those of other seroprevalence studies and with incidence data for the period 1985-2005, calculated by a surveillance system specific for acute viral hepatitis based on symptomatic cases. A total of 3,561 sera, collected by hospital-based reference laboratories in 18 out of 20 Italian Regions, were tested; 1,138 (32%, 95% CI: 30.5-33.5) were positive. The age-adjusted prevalence was 60.1% and the age-specific rates were among the highest rates reported in Europe in the 1990s. The age-adjusted seroprevalence showed a significant north-south gradient, increasing from 55% in northern Italy to 68% in southern Italy. Age and area of residence were found to be strong predictors of previous HAV infection: the marked increase in prevalence with increasing age represents a strong cohort effect. In northern Italy, a marked increase with age was observed beginning with the 20- to 29-year age-class, whereas in southern Italy, such an increase was observed beginning with the 12- to 19-year age-class, indicating that northern Italy preceded southern Italy by 10-20 years in terms of improvements in hygiene and sanitation. The incidence of HAV infection shows an evident peak in 1997, when an outbreak occurred in southern Italy, mainly affecting 15- to 24-year-old individuals. In the period from 1998 to 2005, the incidence drastically decreased (average of 3.2/100,000 inhabitants), reaching a minimum of 2/100,000 inhabitants in 2005.

Rotaviruses (RV) are the most common etiological agents in acute gastroenteritis (GE) in children in the first years of life. Data from the national scientific literature show that RV is responsible of 26% of all cases of hospitalisation for diarrea in children, resulting the most frequently identified agent. The Italian database of hospital discharge, freely available from the web site of the national Ministry of Health, was searched to investigate the epidemiology of RV gastroenteritis. The mean number of hospitalisation for RV enteritis in children in the first 4 years of live was 4.758 in the years 2001, 2002 and 2003, representing 84% of viral enteritis. RV was identified as agent in 17% of all intestinal infectious diseases in this age group. This percentage shows the important role of RV in severe gastrointestinal infections; it is however much lower than the value expected from specifically performed surveys. This underestimation may be attributed to the high number of undefined gastroenteritis found in the database (54%), to the scarce sensitivity of the hospital discharge code, and to the fact that the analysis was performed using only the principal diagnosis. A specific immunisation strategy, safe, effective, cost-effective and easy to perform, could have a great impact on the incidence of the disease and on the associated costs.

Objective: To evaluate the safety and the immunogenicity of a booster dose of recombinant acellular pertussis vaccine combined with diphtheria and tetanus toxoids (DTaP, Biocine SpA) in 15- to 21-month-old children primed in infancy with either whole-cell diphtheria-tetanus-pertussis (DTwP) vaccine or DTaP vaccine. Design: Open-label second phase of a double-masked, controlled trail, with masked analysis of serum samples. Participants and setting: Three hundred fifty children, 15 to 21 months of age, who had been primed at 2, 4, and 6 months of age with either three doses of DTaP vaccine (n = 173) or DTwP vaccine (n = 177). The children were enrolled in eight vaccination centers in Italy. Interventions: All children received a booster dose of the DTaP vaccine and were examined for safety at 48 hours and at 7 days after vaccination. Serum samples for evaluation of immunogenicity were obtained from 196 (55%) of the 350 children. Main outcome measures: IgG antibodies to pertussis toxin (Ptox), filamentous hemagglutinin, 69-kilodalton protein, and tetanus toxoid were measured by enzyme-linked immunosorbent assay. Pertussis toxin-neutralizing antibodies were measured by the Chinese hamster ovary cell toxin neutralization assay. Main results: Adverse reactions to DTaP were infrequent, and there was no difference in the incidence of local or systemic reactions in children given DTaP as a fourth dose in comparison with a first dose. One month after the DTaP booster vaccination, both groups had 6- to 40-fold increases in serum antibody concentrations to all antigens tested; the concentrations against the three pertussis antigens were higher in the DTaP-primed children (p

In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs). The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999. Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M. pneumoniae and C. pneumoniae antibodies. Nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae were obtained on admission. Acute M. pneumoniae infections in 210 patients (34.3%) and acute C. pneumoniae infections in 87 (14.1%) were diagnosed. Fifteen of the 18 children with M. pneumoniae and/or C. pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides. Our study confirms that M. pneumoniae and/or C. pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents.

BACKGROUND: Recently, two Rotavirus (RV) vaccines were licensed in Italy, rendering RV illness a vaccine preventable disease. To assess the RV hospitalization rate in Italy, a study focused on the Regional hospital discharge forms (HDD) databases was carried out. RESULTS: Regional HDD databases from Piemonte, Veneto, Friuli-Venezia-Giulia and Marche were analyzed. A total of 434,335 hospitalizations were counted in the study timeframe and 13,234 VE diagnoses (3% of hospitalizations) were collected. A total of 8546 RVE cases (2% of hospitalizations, 64% of all VE) were observed, of which 1.2% were primary diagnoses (PD) and 0.8% secondary diagnosis (SD). The RVE hospitalization peak (4.9%) was observed at the age of 1 year (4.5% in 7-12 months of age) with a median hospital stay of 4.4 days (s.d +/- 4.2). Two deaths (out of 8546 RVE cases) were identified. PATIENTS AND METHODS: Regional HDD databases with the diagnosis of viral enteritis (VE) and RV enteritis (RVE) (ICD9-CM code 00861-69 and 008.8) in any position of the first 20 discharge diagnoses in children aged less or equal to 5 years between 2001 and 2005 were requested. CONCLUSION: Despite some limitations due to the HDD synthetic contents and low potential for clinical interpretation, the Regional HDD databases, including PD and SD, may be a useful tool for monitoring the clinical impact of RV vaccination introduction in Italy.

CD8 Tcells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 Tcells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 Tcells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 Tcells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 Tcells during active TB. These CD8 Tcells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 Tcells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB.

In 2012, we conducted a retrospective cross-sectional study to assess the number of people living with HIV linked to care and, among these, the number of people on antiretroviral therapy. The health authority in each of the 20 Italian Regions provided the list of Public Infectious Diseases Clinics providing antiretroviral therapy and monitoring people with HIV infection. We asked every Public Infectious Diseases Clinic to report the number of HIV-positive people diagnosed and linked to care and the number of those on antiretroviral therapy during 2012. In 2012, 94,146 people diagnosed with HIV and linked to care were reported. The majority were males (70.1%), Italians (84.4%), and aged between 25 and 49 years (63.4%); the probable route of transmission was heterosexual contact in 37.5% of cases, injecting drug use in 28.1%, and male-to-male contact in 27.9%. Among people in care, 20.1% had less than 350 CD4 cells/μl, 87.6% received antiretroviral therapy, and among these, 62.4% had a CD4 cell count higher than 350 cells/μl. The overall estimated prevalence of individuals diagnosed and linked to care in 2012 in Italy was 0.16 per 100 residents (all ages). Adding the estimated proportion of undiagnosed people, the estimated HIV prevalence would range between 0.19 and 0.26 per 100 residents. In Italy, the majority of people diagnosed and linked to care receive antiretroviral therapy. A higher prevalence of individuals diagnosed and linked to care was observed in Northern Italy and among males. More information for developing the HIV care continuum is necessary to improve the entire engagement in care, focusing on test-and-treat strategies to substantially reduce the proportion of people still undiagnosed or with a detectable viral load.

Th1 CD4(+) T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametic flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-gamma/IL-2/TNF-alpha triple expressors, IFN-gamma/IL-2, IFN-gamma/TNF-alpha or TNF-alpha/IL-2 double expressors or IFN-gamma, IL-2 or TNF-alpha single expressors) of CD4(+) T cells in individuals with latent M. tuberculosis infection (LTBI) and active tuberculosis (TB). We found that triple expressors, while detectable in 85-90%TB patients, were only present in 10-15% of LTBI subjects. On the contrary, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN-gamma double and IFN-gamma single expressors as compared with the other CD4(+) T-cell subsets. Proportions of the other double or single CD4(+) T-cell expressors did not differ between TB and LTBI subjects. These distinct IFN-gamma, IL-2 and TNF-alpha profiles of M. tuberculosis-specific CD4(+) T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB-infected patients after completion of anti-mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4(+) T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti-mycobacterial therapy.

CD8 T-cells contribute to control of Mycobacterium tuberculosis infection, but little is known about the quality of the CD8 T-cell response in subjects with latent infection and in patients with active tuberculosis disease. CD8 T-cells recognizing epitopes from 6 different proteins of Mycobacterium tuberculosis were detected by tetramer staining. Intracellular cytokines staining for specific production of IFN-gamma and IL-2 was performed, complemented by phenotyping of memory markers on antigen-specific CD8 T-cells. The ex-vivo frequencies of tetramer-specific CD8 T-cells in tuberculous patients before therapy were lower than in subjects with latent infection, but increased at four months after therapy to comparable percentages detected in subjects with latent infection. The majority of CD8 T-cells from subjects with latent infection expressed a terminally-differentiated phenotype (CD45RA+CCR7(-)). In contrast, tuberculous patients had only 35% of antigen-specific CD8 T-cells expressing this phenotype, while containing higher proportions of cells with an effector memory- and a central memory-like phenotype, and which did not change significantly after therapy. CD8 T-cells from subjects with latent infection showed a codominance of IL-2+/IFN-gamma+ and IL-2(-)/IFN-gamma+ T-cell populations; interestingly, only the IL-2+/IFN-gamma+ population was reduced or absent in tuberculous patients, highly suggestive of a restricted functional profile of Mycobacterium tuberculosis-specific CD8 T-cells during active disease. These results suggest distinct Mycobacterium tuberculosis specific CD8 T-cell phenotypic and functional signatures between subjects which control infection (subjects with latent infection) and those who do not (patients with active disease).

Serum responses against Mycobacterium tuberculosis HSP16 were determined for children with tuberculosis (TB) and for healthy purified protein derivative (PPD)-positive and PPD-negative children. Immunoglobulin G (IgG) and IgM responses were higher for TB patients than for other groups. After chemotherapy, IgM and IgG responses decreased for TB patients and PPD-positive subjects. Monitoring of anti- M. tuberculosis HSP16 responses could assist in the management of pediatric TB.

Background The severity of childhood gastroenteritis is generally believed to be age-related rather than aetiologyrelated. Rotavirus-induced gastroenteritis is more severe than gastroenteritis caused by other enteric pathogens and is also age-related. We thus addressed the question of whether the increased severity of rotavirus-induced gastroenteritis is related to age or to features intrinsic to the agent. Study design In this multicentre, hospital-based, prospective survey, we evaluated the severity of diarrhoea in rotavirus-positive and rotavirus-negative children up to 4 years of age. Severity was assessed with a score in four groups of age-matched children. Results Rotavirus was detected in 381 of 911 children. Disease severity was evaluated in 589 cases for which clinical data were complete. The rotavirus-positive and rotavirus-negative groups differed with regards to diarrhoea duration, hospital stay, degree of dehydration and the number of episodes of vomiting. Gastroenteritis was more severe in rotavirus-positive than in rotavirus-negative children. In contrast, none of the main severity parameters differed in the four age groups, irrespective of the presence of rotavirus. Conclusions These data provide the evidence that aetiology and not age determines diarrhoeal severity. The demonstration that diarrhoea was more severe in rotavirus-positive children supports the need for a rotavirus vaccine and for studies that address the duration of vaccine protection.

Recent therapeutic approaches have improved the prognosis of children with HIV. Many new efforts could be involved in their quality of life and therefore could need additional diagnostic strategies. Leptin regulates pubertal development; furthermore a continuous immune stimulus, as in chronic infectious diseases, can enhance leptin's secretion by the action of cytokines such as interleukin (IL)-6. To clarify this role in patients infected with HIV, we assayed leptin and IL-6 and evaluated the influence of HIV severity on its secretion. IL-6 (380.5 +/- 257.6 pg/ml; range: 22-900 pg/ml) showed a significant correlation with leptinemia, HIV-1 RNA, and viremia related to the stage of HIV disease. The difference in leptinemia from a control group (3 +/- 3.2 ng/ml; range: 1-12 ng/ml in HIV patients; 6.72 +/- 8 ng/ml in the controls) did not reach statistical significance, nor did it correlate with pubertal stage, BMI, viremia, CD4 or anti-retroviral therapy. There was a statistically significant correlation between leptinemia and the stage of the HIV disease, and with IL-6 level. We want to stress the role of immunological factors in enhancing leptin secretion.

This study evaluated the level of susceptibility of monocytes and lymphocytes to spontaneously induced and CH11-induced apoptosis in 16 patients with Brucella infection. The expression of some immunological and apoptotic markers was evaluated. Before therapy, monocytes showed a high level of resistance to spontaneously induced or CH11-induced apoptosis in all patients. In patients with acute infection, this resistance persisted for 10-20 days after treatment was initiated, then decreased; in chronically infected patients, it persisted after 45 days of treatment. Lymphocytes were also more resistant to CH 11-induced apoptosis. The level of activated CD8++ T lymphocytes was high in patients with acute infection. The data indicate that the CD95-mediated apoptotic pathway is not involved in CH11 resistance. Lymphocytes are not infected by Brucella, so their resistance to apoptosis may be due to a soluble factor released by infected monocytes. The evaluation of levels of susceptibility to CH11-induced apoptosis in monocytes may be used to test the effectiveness of the therapy.

Vgamma9/Vdelta2 T cells can contribute to protective immune response against Mycobacterium tuberculosis, although the extent to which and mechanisms by which they could actually protect against human tuberculosis remain unclear. We have previously reported that Vgamma9/Vdelta2 T cells from tuberculin purified protein derivative (PPD)-positive children, either healthy or affected by different clinical forms of tuberculosis, strongly proliferate to different phosphoantigens in vitro, whereas Vgamma9/Vdelta2 T cells from PPD-negative healthy subjects proliferate very poorly. We report here that Vgamma9/Vdelta2 T cells from tuberculous children have an increased proliferative activity, but decreased interferon (IFN)-gamma production and granulysin expression. After successful chemotherapy, the Vgamma9/Vdelta2 T cell proliferative response strongly decreased, whereas IFN-gamma and granulysin production consistently increased. Disease-associated changes in Vgamma9/Vdelta2 T cell effector functions in patients with tuberculosis are consistent with the possibility that these T cells may play a protective role in immune response against M. tuberculosis infection.

The spectrum of signs and symptoms of 645 consecutive children diagnosed from 1984 to 1996 with boutonneuse fever (BF), a mild rickettsial disease caused by Rickettsia conorii endemic in the Mediterranean basin, are reported. The major clinical features were fever (97.2%), exanthema (96.1%) and “tache noire” (71.8%). The large series examined permitted the authors to observe some rare or disregarded clinical features of the disease: cases with papulovesicular exanthema, reported previously only in adults who had been infected by R. conorii in Africa; and cases in which the only symptom was an isolated lymphadenopathy. Conclusion R. conorii infection should be considered in patients with lymphadenopathy who live in or have travelled to an endemic area, even when other, more specific features, are not present. Also pox-like vesicular lesions may be caused by this organism, awaiting confirmation by using culture techniques instead of serology. The serological confirmation of BF by immuno fluorescent antibody test is possible only late in the illness.

Visceral leishmaniasis (VL) is endemic in Sicily. Although it is a notifiable disease, there is evidence that the actual number of cases is higher than that reported. In 1987, a regional reference center for active surveillance of VL was established and it recorded a total of 284 cases through 1995, a mean of 31.5 cases/year and about four-fold more than previously reported. Of the 284 cases, 150 (53%) were children (≤ 14 years of age), and of the 134 adults, 39 (29%) were coinfected with human immunodeficiency virus (HIV). The commonest viscerotropic zymodeme of Leishmania infantum, MON 1, was identified in 40 (93%) of 43 HIV-negative and eight (57%) of 14 HIV-positive patients. Among 280 patients evaluated (i.e., all HIV-negative and 35 of 39 HIV-positive subjects), 254 (91%) were treated with meglumine antimoniate alone or in combination with other drugs; 23 (8%) received allopurinol or amphotericin B, either conventional or in liposomal form; and three terminally ill patients were not treated. Among the 245 HIV-negative patients, 236 (96%) were successfully cured, while nine (4%) (seven adults) died during the course of antimonial treatment. None of the 35 HIV-positive patients was definitively cured, although mortality was apparently associated with other opportunistic infections.

We studied the immunogenicity of an acellular pertussis vaccine composed of genetically detoxified pertussis toxin (PT-9K/129G), filamentous haemagglutinin, and a 69-kilodalton protein, pertactin, in 30 children aged 12 to 24 months and in 80 infants aged 2 to 4 months. A significant increase of the neutralizing titer and of the titers against pertussis toxin, filamentous hemagglutinin, and pertactin, as determined by enzyme-linked immunosorbent assay, was achieved after three doses of vaccine in all the children; a significant increase of these antibody titers was obtained in 100%, 96.1%, 93.5%, and 98.7% of the infants, respectively.

To determine whether a nontoxic derivative of pertussis toxin obtained by recombinant DNA technology, PT-9K/129G, is a good candidate for a new pertussis vaccine, we examined the safety and the immunogenicity in children of a vaccine containing 15 micrograms of PT-9K/129G protein and 0.5 mg of aluminum hydroxide per dose. Fifty-three children 12 to 24 months of age and 21 infants aged 2 to 4 months were injected with two and three doses, respectively. The vaccine did not induce significant local or systemic reactions and elicited an increase of antibody titer in more than 98% of the children. The geometric mean of the toxin-neutralizing titers increased after each dose and was 85 units in children given two doses and 196 units in those given three doses. Two children who had detectable antibody levels before the first immunization had a high response (greater than 320 units) to the first vaccine dose. The findings suggest that PT-9K/129G is a promising antigen to be included in the development of acellular pertussis vaccines.