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Biomedical subjects

R Dagan

Publications and source records attributed to R Dagan.

At least 19 recordsLinked to original sources

Socioeconomic correlates of antibody levels to enteric pathogens among Israeli adolescents.

We examined the association between socioeconomic status and the level of serum antibodies to selected faeco-orally transmitted pathogens among Israeli adolescents. Random samples of eighty volunteers aged 12-15 years from high (HSL), medium (MSL) and low (LSL) standard of living towns were included in the study. Serum samples were examined by radioimmunoassay for HAV and by in-house-developed ELISA systems for IgA and IgG antibody levels against Shigella sonnei, S. flexneri, E. coli O157:H7 lipopolysacchride and Cryptosporidium parvum antigens. Seropositivity to HAV was highest (98.8%) in the LSL towns and lowest (25%) in the HSL towns, showing a statistically significant linear trend. Antibody levels to the other enteropathogens had gender variation, with higher titres in females. Significantly lower titres in the HSL towns were found for: IgA anti-S. sonnei in females (P<0.001); IgG anti-S. sonnei in females (P=0.024) and males (P=0.033); IgG anti-S. flexneri in females (P=0.016). Inverse linear association with socioeconomic status was found for IgA anti-C. parvum in females (P<0.001); IgA anti-E. coli O157:H7 in females (P<0.001) and males (P=0.024). A statistically significant association between HAV seropositivity and higher titres of IgA anti-S. sonnei and E. coli O157:H7 was shown. In conclusion, exposure to enteropathogens transmitted via the faecal-oral route in communities of lower socioeconomic status is reflected in a higher prevalence of lifelong lasting antibodies to HAV, and higher levels of antibodies to bacterial and protozoan enteropathogens. Among females, the levels of specific serum antibodies are higher and more strongly associated with low socioeconomic status.

Adolescent↗

Use of FTIR spectroscopy to distinguish between capsular types and capsular quantities in Streptococcus pneumoniae.

Fourier transform infrared (FTIR) spectroscopy has shown remarkable ability in distinguishing between bacterial species and identifying bacterial colony structures, when used in tandem with methods such as cluster analysis, principal component analysis, or linear discriminant analysis. The present work was aimed to evaluate the potential of FTIR-microscopy (FTIR-MSP) to distinguish between different serotypes and capsular quantities of Streptococcus pneumoniae. In general, the results obtained have consistently proven that the spectral information at the region 900-1,185 cm(-1) was sufficient to distinguish between various pneumococcal serotypes. Moreover, the method was able to differentiate between S. pneumoniae phase variants on the basis of their relative carbohydrate content. The unsupervised cluster analysis of the samples showed differences, not only in the carbohydrate content, but also in the region 1,350-1,480 cm(-1), which is dominated by absorptions due to lipids and phospholipids. This approach proved to be useful for the distinction between S. pneumoniae serotypes and between phase variants, which were shown to acquire different pathogenic capacity.

Bacterial Capsules↗

Pneumococcal 6-phosphogluconate-dehydrogenase, a putative adhesin, induces protective immune response in mice.

For most bacteria, adherence to human cells is achieved by bacterial lectins binding to mammalian surface glyconjugates. 6-Phosphogluconate dehydrogenase (6PGD) was identified by us as one of Streptococcus pneumoniae cell wall lectin proteins, which elicits an age-dependent immune response in humans. This study assesses the role of 6PGD in S. pneumoniae pathogenesis as an adhesin and its ability to elicit a protective immune response in mice. Recombinant 6PGD (r6PGD) was cloned from S. pneumoniae serotype 3 (strain WU2). r6PGD interference in adhesion of three genetically unrelated unencapsulated pneumococcal strains (3.8, 14.8 and R6) and two genetically unrelated encapsulated pneumococcal strains (WU2 and D39) to A549 type II lung carcinoma cell was tested. BALB/c mice were immunized with r6PGD and boosted after 3 weeks. Immunized mice were challenged intranasally with a lethal dose of S. pneumoniae. r6PGD inhibited 90% and 80% of pneumococcal adhesion to the A549 cells of three unencapsulated S. pneumoniae strains and two encapsulated S. pneumoniae strains, respectively, in a concentration-dependent manner (P < 0.05). Antibodies to r6PGD produced in mice significantly inhibited bacterial adhesion to A549 cell (P < 0.05). Immunization of mice with r6PGD protected 60% (P < 0.001) of mice for 5 days and 40% (P < 0.05) of the mice for 21 days following intranasal lethal challenge. We have identified 6PGD as a surface-located immunogenic lectin protein capable of acting as an adhesin. 6PGD importance to bacterial pathogenesis was demonstrated by the ability of r6PGD to elicit a protective immune response in mice.

Adhesins, Bacterial↗

Virulence of Streptococcus pneumoniae may be determined independently of capsular polysaccharide.

Mice were inoculated intranasally with Streptococcus pneumoniae isolates of serotype 14 with different genetic backgrounds (14R, 14DW) and a capsular switch of 14R, strain 9VR (serotype 9V). Inoculation of the mice with 14R and 9VR resulted in 60% mortality. All the mice survived 14DW inoculation. No differences in lungs' bacterial loads were found 3 h following inoculation. Bacterial clearance of 5 logs was observed 48 h after inoculation with 14DW versus within 1 log 48 h after inoculation with 14R and 9VR. No significant differences in bacterial size or the capsular amount could be found between 14R and 14DW. We conclude that factor(s) in addition to the capsule, contribute to disease outcome.

Animals↗

Acute mastoiditis in infancy: the Soroka experience: 1990-2000.

UNLABELLED: Acute mastoiditis (AM) is an uncommon but serious complication of acute otitis media (AOM). In the pre-antibiotic era, AM was seen more frequently than it is today, but it was rare in infants. However, in the last two decades an increase in the incidence of AM in infancy has been reported in the literature. During the years 1990-2002, we treated 113 patients with 128 episodes of AM; of them, 24 were infants (median age 6 months; 18 males) who suffered from 26 episodes of AM. Twenty developed AM as a complication of their first episode of AOM. One of the four infants with a prior history of AOM suffered from common variable immunodeficiency. A significant increase in the incidence of AM in infants was recorded during the study period (P = 0.01). The most common presenting clinical signs were post-auricular swelling and fever >38 degrees C (77% and 77%, respectively, of all patients). Seventeen episodes of AM were not treated with prior antibiotics. Tympanocentesis was performed in all episodes of AM. Middle ear fluid culture was positive in 17 (65%) of the 26 AM episodes. The most common pathogens cultured were Streptococcus pneumoniae (10 infants, 58% of all pathogens, 3/10 intermediately susceptible to penicillin) followed by Streptococcus pyogenes (4, 23%), non-typable H. influenzae (2, 12%) and S. aureus (1, 6%). Temporal bone CT showed bone destruction in 14 patients; 3 infants had subperiosteal abscesses and 3 lateral sinus thrombosis. Ten infants underwent mastoid surgery due to non-resolution of symptoms and signs with antibiotic therapy. Eight underwent cortical mastoidectomy with two patients undergoing ventilation tube introduction only. The remainder of the infants healed with conservative treatment. CONCLUSIONS: (1) A significant increase in the incidence of AM in infants was recorded over the last decade, though a specific reason for this trend remains uncertain; (2) Most of the cases of AM followed the infant's initial AOM episode, and most of the infants had not received prior antibiotic therapy; (3) The clinical signs and symptoms of AM were more severe in infants than in older patients; (4) While S. pneumonia was the most common pathogen isolated in middle ear fluid cultures, the involvement of S. pyogenes in AM was higher than that reported in AOM.

Abscess↗

Subclinical vitamin A deficiency in Israeli-Bedouin toddlers.

OBJECTIVE: This study was designed to estimate the prevalence of and evaluate risk factors for subclinical vitamin A deficiency in Arab-Bedouin children at age 18 months, followed from birth. DESIGN: Community-based, prospective, cohort study conducted in Rahat, a large Arab-Bedouin township, located near the city of Beer Sheva in the Negev region of southern Israel. SUBJECTS: Healthy Bedouin infants (n=117) from the township, born at Soroka University Medical Center (SUMC) in Beer Sheva, were randomly recruited at birth. Enrollment was restricted to well infants born weighing >2500 g at birth. RESULTS: More than 15% of the children had serum retinol concentrations below 0.7 micromol/l. Male sex (odds ratio (OR) 4.17 [1.14-15.32], P=0.031), stunting at age 12 months (OR 10.09 [2.00-50.97], P=0.05) and warm season at age 18 months (OR 6.20 [1.36-28.28], P=0.018) were associated with vitamin A deficiency. Maternal education decreased the risk of vitamin A deficiency (OR 0.81 [0.68-0.95], P=0.011). CONCLUSIONS: Study results indicate a significant vitamin A deficiency problem among Bedouin children. Deficiency may be prevented by increasing dietary intake of vitamin A, especially during the warm season. Other interventions include preventing and controlling diarrheal diseases in order to avert nutritional stunting, and providing nutritional education to women of childbearing age. SPONSORSHIP: This study received financial support from the National Institute of Allergy and Infectious Diseases (AI-26497), the US-Israel Bi-national Science Foundation (BSF 90-00257), and the National Academy of Sciences/Institute of Medicine (AID/ANE 0158-G-SS-9035-00).

Anthropometry↗

Glycolytic enzymes associated with the cell surface of Streptococcus pneumoniae are antigenic in humans and elicit protective immune responses in the mouse.

Streptococcus pneumoniae is a leading cause of otitis media, sinusitis, pneumonia, bacteraemia and meningitis worldwide. The drawbacks associated with the limited number of various capsular polysaccharides that can be included in the polysaccharide-based vaccines focuses much attention on pneumococcal proteins as vaccine candidates. We extracted an enriched cell wall fraction from S. pneumoniae WU2. Approximately 150 soluble proteins could be identified by 2D gel electrophoresis. The proteins were screened by 2D-Western blotting using sera that were obtained longitudinally from children attending day-care centres at 18, 30 and 42 months of age and sera from healthy adult volunteers. The proteins were further identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Seventeen proteins were antigenic in children and adults, of which 13 showed an increasing antibody response with age in all eight children analysed. Two immunogenic proteins, fructose-bisphosphate aldolase (FBA) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and a control protein with known low immunogenicity, heat shock protein 70 (DnaK), were expressed in Escherichia coli, purified and used to immunize mice. Mouse antibodies elicited to the recombinant (r) FBA and rGAPDH were cross-reactive with several genetically unrelated strains of different serotypes and conferred protection to respiratory challenge with virulent pneumococci. In addition, the FBA used in this study (NP_345117) does not have a human ortholog and warrants further investigation as a candidate for a pneumococcal vaccine. In conclusion, the immunoproteomics based approach utilized in the present study appears to be a suitable tool for identification of novel S. pneumoniae vaccine candidates.

Adult↗

Differential activation of the immune system by virulent Streptococcus pneumoniae strains determines recovery or death of the host.

Streptococcus pneumoniae infection may result in asymptomatic carriage, mucosal or invasive disease. We hypothesize that self-limiting or fatal disease outcome follows infection with S. pneumoniae differential activation of the host immune response. BALB/c and C57BL/6 mice were inoculated intranasally with S. pneumoniae serotype 3 strain WU2 and serotype 14 strain DW14 and mortality, bacterial load, pathological changes in the lungs and cytokines mRNA levels in the spleen were analysed. No differences between the C57BL/6 and the BALB/c inbred mice were observed except for the severity of their lung pathology and IL-4 expression. Infection of the two mouse strains with S. pneumoniae WU2 resulted in sepsis and death that occurred within 4 days post-inoculation. This death was preceded, in both mouse strains, in an increase over time of the lung bacterial load and bacteraemia. The lung pathology was characterized by diffuse pneumonia with marked congestion of the lungs. Analysis of mRNA expression of cytokines in the spleen revealed no alterations in tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, interleukin (IL)-12 and interferon (IFN)-gamma and induction of IL-10 and IL-4. The two strains of mice survived infection with S. pneumoniae DW14. This was accompanied by a reduction over time of lung bacterial load and bacteraemia. The lung pathology was characterized by focal lymphocyte infiltration and preserved architecture of the organ. Analysis of mRNA expression of cytokines in the spleen revealed a significant decrease in the levels of TNF-alpha, TGF-beta, IL-12 and IFN-gamma mRNA expression, which usually precedes cytokine protein expression. Interestingly, a significant increase in the levels of IL-4 mRNA expression was found in BALB/c mice only. This study suggests that differential activation or evasion of cytokine expression by S. pneumoniae virulent strains determines disease outcome regardless of the host's immunogenetic background.

Administration, Intranasal↗

Successful control of an Acinetobacter baumannii outbreak in a neonatal intensive care unit.

We describe an outbreak of Acinetobacter baumannii in a neonatal intensive care unit (NICU), and our investigation to determine the source and mode of transmission and identify the population at risk. A case (infected infant) was defined as a patient hospitalized in the NICU during the outbreak period, with clinical signs of sepsis and isolation of A. baumannii. In colonized infants, A. baumannii was isolated from body surfaces without signs of infection. Infected infants were separated and treated by a different medical team. Cultures were taken from working surfaces and along the infant's admission passage from the delivery room to the NICU. The outbreak strain was identified by pulsed-field gel electrophoresis (PFGE). Nine cases and eight colonized infants met the definition criteria. Cases were younger than colonized infants with regard to gestational age and age of diagnosis and had lower birthweights (P<0.01). The outbreak strain was only isolated from hygroscopic bandages used on skin under the ventilation tube and umbilical catheters. Discontinuing the use of the bandages put an end to the outbreak. We conclude that a rapid and thorough investigation of the environment during an outbreak of A. baumannii is essential to finding the source of the infection, and that hygroscopic bandages may be a source of such outbreaks.

Acinetobacter Infections↗

Klebsiella bacteremia in children in southern Israel (1988-1997).

BACKGROUND: Klebsiella spp. have emerged in recent years as a major cause of gram-negative bacteremia in infants and children. We therefore aimed to document the epidemiology, antibiotic susceptibility pattern and outcome of both community-acquired and nosocomial Klebsiella spp. bacteremias in children. PATIENTS AND METHODS: From 1988-1997, 177 episodes of Klebsiella bacteremia, representing 15% of all gram-negative bacteremias, occurred at the Soroka Medical Center in 166 children aged 0-14 years. RESULTS: The overall incidence of Klebsiella bacteremia in southern Israel during the study period was 0.13/1,000, with an increase from 0.1 to 0.2/1,000 children from 1988-1992 to 1993-1997 (p = 0.02). 113 and 64 episodes were recorded in Bedouin Arabs and Jewish children, respectively. The incidence of Klebsiella bacteremia was significantly higher in Bedouins compared to Jewish children (p < 0.001). The incidence of Klebsiella bacteremia increased significantly among Jewish children from 1993-1997 compared to 1988-1992. The incidence of Klebsiella bacteremia was 2/1,000 admissions, with an increase from 1.8 to 2.2/1,000 from 1993-1997 compared to 1988-1992. The incidence of Klebsiella bacteremia was significantly higher among hospitalized Bedouin children compared to Jewish children (3.1 vs 1.4/1,000 admissions, p < 0.001). There were 48 (27%), 24 (14%) and 98 (55%) Klebsiella bacteremia episodes at the pediatric departments, pediatric intensive care unit (PICU) and neonatal intensive care unit (NICU), respectively. 76% of Klebsiella bacteremia episodes were nosocomial; 66% occurred at NICU. 71% and 90% of Klebsiella bacteremia episodes occurring at NICU and PICU, respectively, were nosocomial. The overall incidence of nosocomial infections was 1.5/1,000 admissions, with an increase from 1.2 to 1.8/1,000 from 1993-1997 compared to 1988-1992 (p = 0.03). The resistance rates of Klebsiella spp. to piperacillin, ceftriaxone, ceftazidime and gentamicin were 34%, 17%, 17% and 14%, respectively. A significant increase in the resistance rates to ceftriaxone and ceftazidime was observed from 1993-1997 compared to 1988-92 (21.9% vs 7.8%, p = 0.05 and 21.9% vs 5%, p = 0.03). A significant increase in resistance to ceftriaxone was recorded at PICU and NICU (from 12% and 0%, respectively, from 1988-1992, to 61% and 16%, respectively, from 1993-1997, p = 0.02). Overall mortality rate of Klebsiella bacteremia was 13% (21/167 cases, 12 and eight at PICU and NICU, respectively). CONCLUSION: An increase in Klebsiella bacteremia was recorded in southern Israel during the 10 years of the study. A marked increase in the rate of nosocomial Klebsiella bacteremia occurred at all departments. Resistance to third-generation cephalosporins emerged frequently at PICU and NICU during the last period of the survey.

Age Distribution↗

Age-dependent preference in human antibody responses to Streptococcus pneumoniae polypeptide antigens.

Vulnerability to Streptococcus pneumoniae is most pronounced in children. The microbial virulence factors and the features of the host immune response contributing to this phenomenon are not completely understood. In the current study, the humoral immune response to separated Strep. pneumoniae surface proteins and the ability to interfere with Strep. pneumoniae adhesion to cultured epithelial cells were analysed in adults and in children. Sera collected from healthy adults recognized Strep. pneumoniae separated lectin and nonlectin surface proteins in Western blot analysis and inhibited on average 80% of Strep. pneumoniae adhesion to epithelial cells in a concentration-dependent manner. However, sera longitudinally collected from healthy children attending day care centres from 18 months of age and over the course of the following 2 years revealed: (a) development of antibodies to previously unrecognized Strep. pneumoniae surface proteins with age; (b) a quantitative increase in antibody responses, measured by densitometry, towards separated Strep. pneumoniae surface proteins with age; and (c) inhibition of Strep. pneumoniae adhesion to epithelial cells, which was 50% on average at 18 months of age, increased significantly to an average level of 80% inhibition at 42 months of age equalling adult sera inhibitory values. The results obtained in the current study, from the longitudinally collected sera from healthy children with documented repeated Strep. pneumoniae colonization, show that repeated exposures are insufficient to elicit an immune response to Strep. pneumoniae proteins at 18 months of age. This inability to recognize Strep. pneumoniae surface proteins may stem from the inefficiency of T-cell-dependent B-cell responses at this age and/or from the low immunogenicity of the proteins.

Adult↗

Immunisation with a pneumococcal 7-valent conjugate vaccine.

Pneumococcal disease causes approximately 1 million deaths a year worldwide in children aged younger than 5 years. Increasing antibiotic-resistant strains have made management of pneumococcal disease difficult. A pneumococcal 7-valent conjugate vaccine (PNCRM7) has been shown to prevent invasive disease in young children; it has also demonstrated a modest impact on the prevention of otitis media. This conjugated vaccine provides a consistent immune response in infants and young children and can be administered simultaneously with other childhood vaccines. It is generally well tolerated, with local reactions similar to those observed with other licensed childhood vaccines. The objective of this review is to discuss the clinical efficacy, immunogenicity and safety of PNCRM7.

Anti-Bacterial Agents↗

Booster response to the tetanus and diphtheria toxoid carriers of 11-valent pneumococcal conjugate vaccine in adults and toddlers.

We measured the tetanus and diphtheria antitoxin responses after administration of one dose of a mixed carrier (tetanus and diphtheria toxoids) 11-valent pneumococcal conjugate vaccine (PncDT) in 20 Finnish adults (mean age 26.1 years) and 20 Finnish (mean age 23.2 months) and 23 Israeli (mean age 18.5 months) toddlers. The vaccinees had previously been immunised with multiple doses of vaccines containing diphtheria and tetanus toxoids. A double-antigen ELISA was used to measure the antitoxin concentrations. PncDT induced significant booster responses in both adults and toddlers to the tetanus and the diphtheria carrier proteins. Thus, the effect on the tetanus and diphtheria immunity of multivalent conjugate vaccines containing tetanus and diphtheria toxoids as carriers needs to be evaluated before such vaccines are routinely implemented.

Adult↗

Avidity and subclasses of IgG after immunization of infants with an 11-valent pneumococcal conjugate vaccine with or without aluminum adjuvant.

Finnish and Israeli infants received an 11-valent mixed-carrier pneumococcal conjugate vaccine with or without aluminum adjuvant at 2, 4, 6, and 12 months of age. The relative avidity of serotype 1-, 5-, 6B-, 14-, 19F-, and 23F-specific IgG antibodies in serum obtained at 7, 12, and 13 months of age was measured by EIA, using thiocyanate as a chaotropic agent. For all serotypes, except 14, avidity increased between the ages of 7 and 12 months. After boosting at 12 months, avidity further increased for all serotypes. The adjuvant improved antibody avidity against serotype 5. The IgG antibodies produced were mainly IgG1 subclass, although some infants also produced IgG2 after boosting. In conclusion, the immunization of infants with this 11-valent pneumococcal conjugate vaccine increased avidity of IgG, suggesting successful immunologic priming.

Adjuvants, Immunologic↗

A decade (1989-1998) of pediatric invasive pneumococcal disease in 2 populations residing in 1 geographic location: implications for vaccine choice.

During 1 decade (1989-1998), data on invasive pneumococcal disease were collected prospectively to assess the burden of disease among Jewish and Bedouin children in southern Israel and the potential reduction in illness that can be achieved by using conjugate vaccines. Data on 513 children <15 years old with bacteriologically proven invasive pneumococcal disease were obtained. Among Jewish and Bedouin children <5 years old, incidence rates were 45 and 139 cases per 100,000 child-years of observation, respectively. Jewish and Bedouin children differed in clinical manifestations, seasonal patterns of disease, serotype distribution, and antibiotic susceptibility rates. The potential coverage by 7-, 9-, and 11-valent conjugate vaccines is 41%, 67%, and 71%, respectively, for Jewish children and 22%, 63%, and 65%, respectively, for Bedouin children. The 9- and 11-valent pneumococcal conjugate vaccines have the potential to substantially decrease invasive pneumococcal disease in southern Israel.

Adolescent↗

Antibiotic-resistant pneumococci carried by young children do not appear to disseminate to adult members of a closed community.

Although antibiotic-resistant pneumococci have been frequently detected among day care center (DCC) attendees, the transmission of these organisms to other members of the community has not been adequately studied. Nasopharyngeal cultures were obtained from 152 children and 244 adult members of a closed community (a kibbutz) in Israel. Serotyping, antibiogram, and pulsed-field gel electrophoresis were performed to determine the relatedness of isolated pneumococci. Twenty (30%) of the 66 isolates from children showed decreased susceptibility to penicillin and 9 isolates (14%) were resistant to > or =3 drugs. Of the 16 isolates from adults, 5 (31%) were intermediately resistant to trimethoprim-sulfamethoxazole. Resistant strains carried by DCC attendees were not isolated either from their parents or from other adult members of the community. Despite the high degree of interpersonal contact occurring in a closed community, resistant pneumococcal strains carried by DCC attendees do not appear to be easily transmitted to the adult population, which suggests the existence of an immunological barrier.

Adolescent↗

Antibiotic treatment in acute Otitis Media promotes superinfection with resistant Streptococcus pneumoniae carried before initiation of treatment.

Antibiotic-resistant pneumococci are difficult to eradicate from middle ear fluid (MEF) and the nasopharynx (NP). Bacteriologic eradication from the NP and MEF during acute otitis media (AOM) by 3 common antibiotic drugs was prospectively evaluated. In 19 (16%) of 119 MEF culture-positive patients, an organism susceptible to the treatment drug (Haemophilus influenzae, Streptococcus pneumoniae, or both) was isolated from the initial MEF, whereas resistant S. pneumoniae was present in the NP; in 9 (47%) patients, the initial resistant NP organism (identified by serotyping, resistance to the administered drug, and pulsed-field gel electrophoresis) replaced the susceptible MEF organism within only a few days after initiation of treatment. In regions where resistant pneumococci are prevalent, antibiotics may not only fail to eradicate the organisms, but they may often induce MEF superinfection with resistant pneumococci initially carried in the NP. This is an important mechanism by which, in recently treated patients, AOM infections often become refractory to treatment.

Acute Disease↗

Cryptosporidium infection in Bedouin infants assessed by prospective evaluation of anticryptosporidial antibodies and stool examination.

An enzyme-linked immunosorbent assay system using oocyst lysate as antigen was used to detect serum- specific antibody responses to Cryptosporidium parvum between 1989 and 1994 in consecutive sera obtained at birth, and at the age of 6, 12, and 23 months, from 52 infants living in a Bedouin town located in the south of Israel. The serologic tests revealed high levels of immunoglobulin G anti-Cryptosporidium at birth that dropped significantly by the age of 6 months and then rose continuously to a geometric mean titer of 481 at age 23 months. The serum immunoglobulin M Cryptosporidium antibodies rose continuously from nearly undetectable levels at birth to a geometric mean titer of 471 (157-fold increase) at age 23 months. All the subjects already showed at 6 months a significant rise in immunoglobulin M. A significant rise in immunoglobulin A titers was detected in 48% and 91% of subjects at 6 and 23 months, respectively. By monthly surveillance, microscopy using the modified Ziehl-Neelsen method and confirmed by indirect immunofluorescence assay detected Cryptosporidium antigens in only 11% at age 6 months and 48% at age 23 months. The extent of exposure to Cryptosporidium immediately after birth as detected by serology is much higher than that predicted by frequent prospective assessment of stool samples.

Adult↗