Int J Infect Dis, 2003 Jun, 7(2), 143 - 51 Facilitating the WHO expanded program of immunization: the clinical profile of a combined diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type b vaccine; Aristegui J et al.; BACKGROUND: Vaccines are important weapons in the fight against infectious diseases . The World Health Organization (WHO) Expanded Program on Immunization (EPI) has been extended to include recommendations for hepatitis B and Haemophilus influenzae type b (Hib) vaccinations . The WHO has recommended that combined vaccines be used where possible, to reduce the logistic costs of vaccine delivery . This paper reviews the efficacy, safety and cost-effectiveness of Tritanrix-HB/Hib, the only commercially available combined diphtheria, tetanus, whole cell pertussis, hepatitis B and conjugated Hib vaccine . METHODS: The immunogenicity and reactogenicity results of five published clinical trials involving Tritanrix-HB/Hib in a variety of immunization schedules and countries were reviewed . Based on these data and cost-effectiveness studies, an assessment of its suitability for use in national immunization programs was made . RESULTS: Tritanrix-HB/Hib has shown excellent immunogenicity in clinical trials using a variety of schedules, with no reduced immunogenicity observed for any of the components of the combined vaccine . It has similar reactogenicity to DTPw vaccines alone . Pharmacoeconomic analyses have shown combined DTP-HB/Hib vaccines to be cost-effective compared to separate vaccines . CONCLUSIONS: Replacement of DTPw vaccination by Tritanrix-HB/Hib can be done without modifying the existing national immunization programs . This should facilitate widespread coverage of hepatitis B and Hib vaccinations and their rapid incorporation into the EPI. Int J Infect Dis, 2003 Jun, 7(2), 109 - 12 Childhood bacterial meningitis in Bulgaria: a population-based retrospective study in six regions during 1992-96; Kojouharova M et al.; OBJECTIVES: We conducted a study to provide information on the importance of bacterial pathogens causing childhood meningitis in Bulgaria . METHODS: A 5-year population-based retrospective survey for bacterial meningitis in children <5 years of age was performed at all hospitals in the six largest regions of Bulgaria . RESULTS: There were 297 cases of meningitis reported, of which 211 (71.0%) were classified as bacterial in origin . The most common causes were Neisseria meningitidis (49 cases) and Haemophilus influenzae type b (Hib) (44 cases), accounting for 36% and 32% of etiologically confirmed cases . Thirty-one cases (70.5%) of Hib meningitis occurred in children <2 years of age, and 26 (59.1%) occurred in children 6-23 months of age . Average annual incidence rates of Hib meningitis based on the population of children <5 years of age for each region ranged from 1.3 to 9.8 per 100,000 (mean 5.9/100,000) . CONCLUSION: The estimated incidence rates from this study were similar to those reported from southern European and Mediterranean countries . Further studies are planned to provide information on appropriate strategies for preventing childhood meningitis in Bulgaria. Int J Infect Dis, 2003 Mar, 7 Suppl 1, S27 - 31 Implications for antimicrobial prescribing of strategies based on bacterial eradication; Klugman KP; Antimicrobial prescribing in respiratory tract infection is generally empirical . Agents that do not eradicate the key bacterial respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) provide suboptimal therapy . A recent paper developed by a multidisciplinary, multinational group presented a consensus on the principles that should underpin appropriate antimicrobial prescribing . In summary, in order to ensure clinical success and minimize the threat of resistance, empirical therapy should avoid unnecessary and inappropriate use of antimicrobials, deliver the right agent at the right dose and duration, and rapidly eradicate the pathogen at the site of infection . Accurate diagnosis is essential to ensure that only bacterial infections are treated with antibacterial agents . The application of pharmacokinetic/pharmacodynamic (PK/PD) principles to both new and existing antimicrobials allows the prediction of bacteriologic efficacy . Applying these principles when prescribing therapy can help in reducing the potential for the selection and spread of resistance . Local resistance patterns and the bacteriologic/clinical impact of resistance should also be considered . The use of antimicrobials with optimal PK/PD characteristics may be more cost-effective than allowing the possibility of resistance-induced failure . Changing prescribing habits without taking all these factors into account may increase the incidence of unfavorable patient outcomes and the cost of treatment, with more referrals and hospitalizations . Changes in prescribing habits should be considered carefully, to avoid unintended negative consequences . It is the responsibility of physicians to ensure that each prescription is necessary and will maximize the potential for clinical cure, but there is also a collective responsibility to sustain the diversity of antimicrobial therapy via appropriate formularies, guidelines and licensing, reduced over-the-counter availability, and continued research and development through academia and industry . To maximize clinical cure and minimize the emergence and spread of resistance, antimicrobial prescribing should maximize bacterial eradication, and clinical drug evaluation needs to be brought into line with this need. Int J Infect Dis, 2003 Mar, 7 Suppl 1, S21 - 6 Achieving bacterial eradication using pharmacokinetic/pharmacodynamic principles; Dagan R; Evidence from studies in otitis media indicates that antimicrobials and dosing regimens that have equivalent bacteriologic efficacy against susceptible pathogens can have significantly different bacteriologic success rates against resistant strains of the same species . Unlike macrolide and fluoroquinolone resistance, penicillin resistance can be overcome in Streptococcus pneumoniae by increasing the dose, and hence increasing the time for which the serum concentrations are above the MIC . The new clinical formulation of extra-strength amoxicillin-clavulanate provides 90 mg/kg per day amoxicillin plus 6.4 mg/kg per day clavulanate (14:1) divided every 12 h, compared with 45/6.4 mg/kg per day b.i.d . with conventional dosing . The pharmacokinetic/pharmacodynamic (PK/PD) profiles of extra-strength amoxicillin-clavulanate predict that the new formulation will be more effective than the conventional formulation against S . pneumoniae with elevated amoxicillin MICs and against Haemophilus influenzae . In an open-label, non-comparative study in children with acute otitis media, the extra-strength formulation had high bacteriologic success rates against the major respiratory pathogens, including penicillin-resistant S . pneumoniae . The development of new antimicrobial agents and formulations should be aimed at meeting PK/PD parameters predictive of bacterial eradication of both susceptible and resistant strains. Acta Paediatr, 2003 May, 92(5), 541 - 5 Immunogenicity and safety in infants of a DTwPHib full liquid vaccine; Botet Asensi FI et al.; AIM: Combining paediatric vaccines is a rational solution to reduce the number of injections during a single clinical visit, to maintain parents' compliance and to extend vaccine coverage . Different diphtheria, tetanus and whole cell pertussis (DTwP)-containing combination vaccines are licensed and used world-wide . This study assessed the immunogenicity and safety in infants of a combined diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b-CRM197 conjugate full liquid vaccine . METHODS: The safety and efficacy of a combined ready-to-use liquid vaccine containing diphtheria and tetanus toxoids, cell suspension of Bordetella pertussis and H . influenzae type b-CRM197 conjugate vaccine (DTwPHib) were assessed in infants eligible for the local Expanded Programme on Immunization (EPI) in Valencia, Spain . The comparative group received separate injections of reference vaccines DTwP + Hib . RESULTS: Local and systemic reactions and adverse events were generally mild and similar in the two groups . DTwPHib elicited anti-PRP antibody titres > or = 0.15 microg ml(-1) in 97% and DTwP + Hib in 94% of infants . Furthermore, 89% of DTwPHib and 78% of DTwP + Hib recipients attained anti-PRP antibody titres > or = 1.0 microg ml(-1), signifying long-term protection . The anti-PRP geometric mean titre was significantly higher in the combined DTwPHib vaccine group (6.65 vs 3.57 microg ml(-1)) . In both groups, 99% of infants achieved protective (> or = 0.01 IU ml(-1)) anti-diphtheria antibody levels and all children achieved protective (> or = 0.1 IU ml(-1)) anti-tetanus antibody levels . DTwPHib caused a > or = 2-fold increase in anti-pertactin antibody titres in 91% and a > or = 4-fold increase in 82% of recipients . The corresponding proportions in the DTwP + Hib group were 95% and 90% . DTwPHib induced a > or = 2-fold increase in anti-Aggl2 and 3 antibody levels in 79% and a > or = 4-fold increase in 73% of recipients . The corresponding proportions among DTwP + Hib infants were 85 and 82% . CONCLUSION: Overall, the combined liquid vaccine DTwPHib is a safe and effective immunogenic vaccine for EPI use in infants. Mikrobiyol Bul, 2003 Jan, 37(1), 19 - 25 {In vitro sensitivity to antimicrobial agents of Haemophilus influenzae strains isolated from clinical specimens}; Budak F et al.; In-vitro activity of several antimicrobial agents were evaluated against Haemophilus influenzae (n:127) isolated from clinical specimens within the years 2000 and 2002 in a children's hospital . Antimicrobial susceptibility tests were performed by disk diffusion method according to the recommendations of the NCCLS standards and beta-lactamase activity was investigated by nitrocefin test . Resistance rates for the antibiotics were as follows: ampicillin 5.6%, trimethoprim-sulfamethoxazole (TMP/SMX) 27.5%, tetracycline 8.6%, clarithromycin 7%, chloramphenicol 4.7% . Five isolates (3.9%) were found multiple resistant . Beta-lactamase activities were detected in all of the ampicillin resistant isolates . None of the isolates were resistant to ampicillin-sulbactam, cefaclor, cefuroxime, cefprozil, cefpodoksim, cefotaxime, meropenem or ciprofloxacin . According to these results, resistance to ampicillin is low in our H . influenzae isolates compared to other European countries but resistance to TMP/SMX is very high and this finding has to be taken into account in the empirical therapy of community acquired respiratory tract infections. Bone Marrow Transplant, 2003 Jul, 32(2), 225 - 9 Polysaccharide antibody responses are impaired post bone marrow transplantation for severe combined immunodeficiency, but not other primary immunodeficiencies; Slatter MA et al.; Established treatment of severe combined immunodeficiencies (SCID) and other primary immunodeficiencies (PID) is bone marrow transplantation (BMT) . Normal lymphocyte numbers and protein antigen responses are present within 2 years of BMT, polysaccharide antibody responses appear last . Streptococcus pneumoniae infection causes significant morbidity and mortality post-BMT . Previous studies have shown good protein antigen responses post-BMT for SCID and PID, but had not examined the polysaccharide responses . We retrospectively analysed pneumococcal polysaccharide (PPS) responses in our patient series.In total, 22 SCID and 12 non-SCID PID were evaluated, all >2 years post BMT: 17 SCID, 12 PID received chemotherapy conditioning; 17 SCID, three PID had T-cell depleted (TCD) BMT, others had nonconditioned whole marrow BMT . All had normal Haemophilus influenza B and tetanus antibody responses . Of 22 SCID, 13 vs 11/12 PID responded to PPS vaccine (P=0.05) . There was no association with donor age, GvHD, B-cell chimerism, or IgG2 level . Fewer TCD marrow recipients responded to PPS (P=0.04) . Analysis of the SCID group showed no association of PPS response with type of marrow received . This is the first study to specifically examine PPS antibody responses following SCID and PID BMT . Pneumococcal conjugate vaccine antibody responses should be examined in these children. Pediatrics, 2003 Jul, 112(1 Pt 1), e39 - 45 The immunization delivery effectiveness assessment score: a better immunization measure? Glauber JH. BACKGROUND: Childhood immunization measures, such as the Health Employer Data Information Set (HEDIS) or the National Immunization Survey, assess the percentage of children up-to-date for a specified series of vaccinations . In particular, the HEDIS assesses immunization delivery to children enrolled in managed care organizations (MCO) . Such measures do not assess the timeliness of immunization delivery with reference to recommended age standards . To achieve maximal protection against vaccine-preventable diseases, children should receive all immunizations within recommended age intervals-fully "on-time." OBJECTIVE: The Immunization Delivery Effectiveness Assessment (IDEA) is a novel immunization measure that assesses, on a continuous scale, the timeliness of administration of each vaccination with reference to recommended age intervals . Specifically we ask: 1) Do absolute immunization rates differ between HEDIS and IDEA? 2) Does relative MCO performance differ when assessed by the 2 performance measures? 3) How well do MCOs perform relative to the standard of fully on-time immunization? The health services implications of using the timeliness standard to assess childhood immunization delivery is discussed . METHODS: A vaccine-dose IDEA score was developed for each of the 14 vaccination events in the 4:3:1:3:3 combination series (4 diphtheria-pertussis-tetanus:3 polio:1 measles-mumps-rubella:3 Haemophilus influenzae type B:3 hepatitis B) . Assessing the actual age of administration with reference to the recommended age of administration generates the vaccine-dose IDEA score . A child's composite IDEA score is obtained by averaging the 14 vaccine-dose IDEA scores . These composite IDEA scores, when averaged among children sampled within the MCO, constitute the MCO's immunization score . SETTING: Retrospective analysis of childhood immunization datasets from a convenience sample of 6 MCOs in 5 states . RESULTS: HEDIS rates ranged from 57% to 75% . IDEA scores ranged from 80% to 90% . Relative rankings of MCO immunization performance were different using HEDIS rates and IDEA scores, respectively . At most, 16% of children in any of these MCOs received all of their immunizations fully on-time . From 47% to 77% of children experienced at least 3 delayed immunizations . CONCLUSIONS: An immunization measure based on timeliness of administration yields both absolute and relative differences in MCO childhood immunization performance when compared with HEDIS rates . By assessing delivery of each component vaccination, the IDEA score permits more detailed analysis of immunization patterns within an MCO and focuses improvement efforts. Pediatrics, 2003 Jul, 112(1 Pt 1), 193 - 8 Immunization of preterm and low birth weight infants . American Academy of Pediatrics Committee on Infectious Diseases; Saari TN; American Academy of Pediatrics Committee on Infectious Diseases; Preterm (PT) infants are at increased risk of experiencing complications of vaccine-preventable diseases but are less likely to receive immunizations on time . Medically stable PT and low birth weight (LBW) infants should receive full doses of diphtheria, tetanus, acellular pertussis, Haemophilus influenzae type b, hepatitis B, poliovirus, and pneumococcal conjugate vaccines at a chronologic age consistent with the schedule recommended for full-term infants . Infants with birth weight less than 2000 g may require modification of the timing of hepatitis B immunoprophylaxis depending on maternal hepatitis B surface antigen status . All PT and LBW infants benefit from receiving influenza vaccine beginning at 6 months of age before the beginning of and during the influenza season . All vaccines routinely recommended during infancy are safe for use in PT and LBW infants . The occurrence of mild vaccine-attributable adverse events are similar in both full-term and PT vaccine recipients . Although the immunogenicity of some childhood vaccines may be decreased in the smallest PT infants, antibody concentrations achieved usually are protective. J Bacteriol, 2003 Jul, 185(14), 4152 - 62 Crystal structures of active fully assembled substrate- and product-bound complexes of UDP-N-acetylmuramic acid:L-alanine ligase (MurC) from Haemophilus influenzae; Mol CD et al.; UDP-N-acetylmuramic acid:L-alanine ligase (MurC) catalyzes the addition of the first amino acid to the cytoplasmic precursor of the bacterial cell wall peptidoglycan . The crystal structures of Haemophilus influenzae MurC in complex with its substrate UDP-N-acetylmuramic acid (UNAM) and Mg(2+) and of a fully assembled MurC complex with its product UDP-N-acetylmuramoyl-L-alanine (UMA), the nonhydrolyzable ATP analogue AMPPNP, and Mn(2+) have been determined to 1.85- and 1.7-A resolution, respectively . These structures reveal a conserved, three-domain architecture with the binding sites for UNAM and ATP formed at the domain interfaces: the N-terminal domain binds the UDP portion of UNAM, and the central and C-terminal domains form the ATP-binding site, while the C-terminal domain also positions the alanine . An active enzyme structure is thus assembled at the common domain interfaces when all three substrates are bound . The MurC active site clearly shows that the gamma-phosphate of AMPPNP is positioned between two bound metal ions, one of which also binds the reactive UNAM carboxylate, and that the alanine is oriented by interactions with the positively charged side chains of two MurC arginine residues and the negatively charged alanine carboxyl group . These results indicate that significant diversity exists in binding of the UDP moiety of the substrate by MurC and the subsequent ligases in the bacterial cell wall biosynthesis pathway and that alterations in the domain packing and tertiary structure allow the Mur ligases to bind sequentially larger UNAM peptide substrates. J Bacteriol, 2003 Jul, 185(14), 4144 - 51 The crystal structure of shikimate dehydrogenase (AroE) reveals a unique NADPH binding mode; Ye S et al.; Shikimate dehydrogenase catalyzes the NADPH-dependent reversible reduction of 3-dehydroshikimate to shikimate . We report the first X-ray structure of shikimate dehydrogenase from Haemophilus influenzae to 2.4-A resolution and its complex with NADPH to 1.95-A resolution . The molecule contains two domains, a catalytic domain with a novel open twisted alpha/beta motif and an NADPH binding domain with a typical Rossmann fold . The enzyme contains a unique glycine-rich P-loop with a conserved sequence motif, GAGGXX, that results in NADPH adopting a nonstandard binding mode with the nicotinamide and ribose moieties disordered in the binary complex . A deep pocket with a narrow entrance between the two domains, containing strictly conserved residues primarily contributed by the catalytic domain, is identified as a potential 3-dehydroshikimate binding pocket . The flexibility of the nicotinamide mononucleotide portion of NADPH may be necessary for the substrate 3-dehydroshikimate to enter the pocket and for the release of the product shikimate. J Bacteriol, 2003 Jul, 185(14), 4031 - 7 Crystal structure of the YchF protein reveals binding sites for GTP and nucleic acid; Teplyakov A et al.; The bacterial protein encoded by the gene ychF is 1 of 11 universally conserved GTPases and the only one whose function is unknown . The crystal structure determination of YchF was sought to help with the functional assignment of the protein . The YchF protein from Haemophilus influenzae was cloned and expressed, and the crystal structure was determined at 2.4 A resolution . The polypeptide chain is folded into three domains . The N-terminal domain has a mononucleotide binding fold typical for the P-loop NTPases . An 80-residue domain next to it has a pronounced alpha-helical coiled coil . The C-terminal domain features a six-stranded half-barrel that curves around an alpha-helix . The crablike three-domain structure of YchF suggests the binding site for a double-stranded nucleic acid in the cleft between the domains . The structure of the putative GTP-binding site is consistent with the postulated guanine specificity of the protein . Fluorescence measurements have demonstrated the ability of YchF to bind a double-stranded nucleic acid and GTP . Taken together with other experimental data and genomic analysis, these results suggest that YchF may be part of a nucleoprotein complex and may function as a GTP-dependent translation factor. FEMS Immunol Med Microbiol, 2003 Jul 15, 37(2-3), 185 - 92 Construction of recombinant S-layer proteins (rSbsA) and their expression in bacterial ghosts--a delivery system for the nontypeable Haemophilus influenzae antigen Omp26; Riedmann EM et al.; This study has investigated the feasibility of a combination of recombinant surface layer (S-layer) proteins and empty bacterial cell envelopes (ghosts) to deliver candidate antigens for a vaccine against nontypeable Haemophilus influenzae (NTHi) infections . The S-layer gene sbsA from Bacillus stearothermophilus PV72 was used for the construction of fusion proteins . Fusion of maltose binding protein (MBP) to the N-terminus of SbsA allowed expression of the S-layer in the periplasm of Escherichia coli . The outer membrane protein (Omp) 26 of NTHi was inserted into the N-terminal and C-terminal regions of SbsA . The presence of the fused antigen Omp26 was demonstrated by Western blot experiments using anti-Omp26 antisera . Electron microscopy showed that the recombinant SbsA maintained the ability to self-assemble into sheet-like and cylindrical structures . Recombinant E . coli cell envelopes (ghosts) were produced by the expression of SbsA/Omp26 fusion proteins prior to gene E-mediated lysis . Intraperitoneal immunization with these recombinant bacterial ghosts induced an Omp26-specific antibody response in BALB/c mice . These results demonstrate that the NTHi antigen, Omp26, was expressed in the S-layer self-assembly product and this construct was immunogenic for Omp26 when administered to mice in bacterial cell envelopes. J Endotoxin Res, 2003, 9(3), 131 - 44 The lipo-oligosaccharides of Haemophilus influenzae: an interesting array of characters; Swords WE et al.; The composition of the lipo-oligosaccharide (LOS) of Haemophilus influenzae is highly variable, especially in the oligosaccharide region . Many of the biosynthetic and transferase genes involved in LOS biosynthesis vary in seemingly random fashion by means of polymerase stuttering within redundant sequences in the 5'-portion of the genes . This results in a heterogeneous population of individual bacteria expressing literally thousands of LOS glycoforms . The simultaneous variation in the expression and structural context of a large number of individual carbohydrate and lipid structures within the LOS yields a diverse array of LOS glycoforms . The expression of glycoforms that mimic host structures may allow the organism to evade innate defenses and to manipulate host cell biology . We review how this randomly generated bacterial combinatorial chemistry results in the production of a large number of carbohydrate structures, in essentially any conceivable structural context, some of which allow the organism to utilize host cell receptors . By generating a diverse population of bacteria expressing different LOS glycoforms, discrete H . influenzae subpopulations may be adapted for survival of different environmental stresses within the airways . Thus, H . influenzae utilizes a simple and efficient "Monte Carlo" strategy for achieving maximal variation in cell surface structures, which allow the organism to adapt efficiently to environmental stresses with a small genome. Pediatr Int, 2003 Jun, 45(3), 314 - 8 Effect of aluminum adjuvants on safety and immunogenicity of Haemophilus influenzae type b-CRM197 conjugate vaccine; Kanra G et al.; OBJECTIVE: The present study was carried out to evaluate the safety and immunogenicity of the Haemophilus influenzae type b-CRM197 (Hib-CRM197) conjugate vaccine in relation to the change of adjuvant from aluminum hydroxide to aluminum phosphate (AlPO4) . METHODS: The present study was a clinical phase II, observer-blind, randomized, multicenter, controlled study . Subjects were healthy infants aged 6-12 weeks, eligible for expanded program of immunization (EPI) routine vaccination and admitted to Hacettepe University Department of Social Pediatrics and Gulveren Health Center, Ankara . A total of 520 healthy infants were randomized in a 2:2:1 ratio to receive at either Chiron Hib/AlPO4 vaccine or VaxemHib (aluminum hydroxide adjuvant) vaccine or HibTiter (no adjuvant) . Vaccines were administered simultaneously with routine diphtheria, tetanus and pertussis (DTaP) and oral polio vaccine (OPV) vaccines at 2, 4 and 6 months of age . Blood samples for anti-plain polysaccharide (PRP) antibody measurement were collected before the first vaccination and 1 month after the last vaccination . After each vaccination parents filled out a diary for 7 days . RESULTS: Out of 520 subjects enrolled, 514 received three doses and were included for safety analysis . Local and systemic reactions occurred with low and similar frequencies in all groups . Only erythema was more common in Chiron Hib/AlPO4 vaccine (19, 10, 11% in Chiron Hib/AlPO4, VaxemHib and HibTiter, respectively, P < 0.05) . Nine serious adverse events were reported in seven cases of which none were related to vaccines . A total of 504 subjects were included in the immunogenicity analysis . The three vaccines were highly immunogenic and equivalent in terms of percentage of acquisition of long-term protective levels . The anti-PRP geometric mean titers were 9.9, 8.3 and 5.14 micro g/mL, respectively (P < 0.05) . CONCLUSIONS: The use of aluminum compounds adjuvants in Hib-CRM197 conjugate vaccines does not impact the safety profile, while it does increase the magnitude of anti-PRP antibody titers. Lancet, 2003 Jun 21, 361(9375), 2139 - 48 Bacterial meningitis in children; Saez-Llorens X et al.; This review comprises aspects of the epidemiology, microbiology, pathophysiology, clinical manifestations, diagnosis, management, prognosis, and prevention of bacterial meningitis, with emphasis on the paediatric population . The beginning of this millennium has witnessed the virtual disappearance of Haemophilus invasive disease in some countries, emergence of pneumococcal strains that are resistant to multiple antibiotics, isolation of pneumococci with tolerance to vancomycin, outbreaks and clusters of meningococcal meningitis in several geographical areas, and intense research in development of effective conjugate pneumococcal and meningococcal vaccines . Bacterial meningitis has become an uncommon disease in the developed world . Unfortunately, because of limited economic resources and poor living conditions, many developing countries are still affected by the devastating consequences of this life-threatening systemic infection . Basic and clinical research is needed to discover new antimicrobial and anti-inflammatory agents to improve outcome from disease . Novel strategies are needed to distribute and implement effective vaccines worldwide to prevent bacterial meningitis. J Infect Dis, 2003 Jul 1, 188(1), 114 - 7 Epub 2003 Jun 23. Horizontal transfer of the gene encoding outer membrane protein P2 of nontypeable Haemophilus influenzae, in a patient with chronic obstructive pulmonary disease; Hiltke TJ et al.; An adult with chronic obstructive pulmonary disease was monitored prospectively for 2 years . Nontypeable Haemophilus influenzae was isolated from sputum cultures at 22 of 23 monthly clinic visits . Analysis of the isolates, by pulsed-field gel electrophoresis (PFGE), revealed that the patient was colonized by 3 different strains during the 2-year period . The gene encoding outer-membrane protein (OMP) P2, ompP2, was amplified from sputum samples and selected strains obtained from this patient . Analysis of the ompP2 sequences, in combination with the PFGE patterns, indicated that ompP2 horizontal transfer between 2 strains occurred in the respiratory tract, between clinic visits 13 and 14 . Observation of ompP2 horizontal transfer in the human respiratory tract has important implications for both the understanding of ompP2 diversity among strains and the future design of OMP P2-based vaccines. J Infect Dis, 2003 Jul 1, 188(1), 74 - 80 Epub 2003 Jun 23. Implications of Haemophilus influenzae biogroup aegyptius hemagglutinins in the pathogenesis of Brazilian purpuric fever; Barbosa SF et al.; Brazilian purpuric fever (BPF) is an acute disease caused by Haemophilus influenzae biogroup aegyptius; it is characterized by fever, purpura, and hypotensive shock and is usually fatal . The factors responsible for bacterial virulence and pathogenesis are poorly known . Hemagglutinins have been frequently associated with bacterial virulence, and, in the present study, hemagglutinating activity was detected in extracellular products from H . influenzae biogroup aegyptius strains isolated from patients with BPF . A 60-kilodalton (kDa) molecule absorbable by human O-type erythrocytes was identified by an immunoblot assay; a corresponding fraction was chromatographically purified, and its pathogenic effect was evaluated . Rabbits injected intravenously with either the whole bacterial extracellular product or the 60-kDa fraction showed reactions similar to those seen in patients with BPF: purpura, congestion, and fibrin thrombi in the inner organs . We suggest that this hemagglutinating factor is one of the major pathogenic components of BPF. Mol Microbiol, 2003 Jul, 49(1), 241 - 9 Species specificity in the activation of Xer recombination at dif by FtsK; Yates J et al.; In Escherichia coli, chromosome dimers are resolved to monomers by the addition of a single cross-over at a specific locus on the chromosome, dif . Recombination is performed by two tyrosine recombinases, XerC and XerD, and requires the action of an additional protein, FtsK . We show that Haemophilus influenzae FtsK activates recombination by H . influenzae XerCD at H . influenzae dif . However, it cannot activate recombination by E . coli XerCD . Reciprocally, E . coli FtsK cannot activate recombination by the H . influenzae recombinases at H . influenzae dif . We took advantage of this species specificity to gain further insight into the mechanism of activation of Xer recombination at dif by FtsK . We mapped the region of FtsK implicated in species specificity to the extreme 140-amino-acid C-terminal residues of the protein . Our results suggest that FtsK interacts directly with XerCD in order to activate recombination at dif. Oral Microbiol Immunol, 2003 Aug, 18(4), 256 - 9 Characterization and expression of adjacent proline iminopeptidase and aspartase genes from Eikenella corrodens; Selby T et al.; Two adjacent genes involved in nitrogen metabolism from Eikenella corrodens, with a potential role in pathogenesis, were studied . Proline iminopeptidase (Pip) activity, which may be essential for energy production and protection against host immune mechanisms, is exhibited by E . corrodens . Analysis of Pip-expressing clones revealed an ORF of 939 bases with a predicted amino acid sequence identity of 67% to the Pip of Neisseria gonorrhoea . 200 bp downstream from pip, an ORF of 1395 bases, encoding a protein with 87% identity to a putative aspartase from the Neisseria meningitidis genome sequence, was identified . Enzymatic function was confirmed with a complemented Escherichia coli aspartase deficient mutant . The E . corrodens aspartase was found to be 77% identical to the Haemophilus influenzae aspartase sequence, which was originally identified on the basis of its ability to bind plasminogen . However, the E . corrodens aspartase had no such activity . Southern hybridization indicated both genes to be single copy and conserved within the genomes of a diverse panel of E . corrodens isolates from health and disease. J Laryngol Otol, 2003 Jun, 117(6), 449 - 53 Increased antimicrobial resistance in organisms recovered from otitis media with effusion; Brook I et al.; Previous studies concerning the microbiology of otitis media with effusion (OME) did not correlate the past use of antimicrobial agents with the recovered organism's antimicrobial susceptibility . A retrospective analysis of cultures obtained from aspirates of 129 children with OME was performed . The study identified the isolated organisms and determined their susceptibility to the most recently administered antimicrobials . Bacterial growth was noted in 58 (45 per cent) patients . Aerobic organisms only were recovered in 37 aspirates (63 per cent of the culture-positive aspirates); anaerobic bacteria in seven (12 per cent); and mixed aerobic and anaerobic bacteria in 14 (24 per cent) . A total of 92 bacterial isolates were recovered, accounting for 1.6 isolates per specimen (1.1 aerobes and 0.5 anaerobes) . There were a total of 66 aerobic isolates, including Haemophilus influenzae non type-b (20 isolates), Streptococcus pneumoniae (17), and Staphylococcus spp . (seven) . Twenty-six anaerobes were recovered, including Peptostreptococcus spp . and Prevotella spp . (eight each) and Propionibacterium acnes (four) . Resistance to the antimicrobial used was found in 60 (65 per cent) isolates, recovered from 41 (71 per cent) of the patients . Of the 41 patients in whom resistance was detected, 37 (90 per cent) had been treated within three months of culture and four (10 per cent) had completed treatment more than three months before the cultures were taken (p < 0.01) . The highest rate of recovery of resistant organisms was following trimethoprim-sulfamethoxazole (96 per cent), amoxycillin (71 per cent), and azithromycin (56 per cent) . Of the patients treated with amoxycillin, H influenzae predominated . S pneumoniae was recovered from four of the seven (57 per cent) after trimethoprim-sulfamethoxazole, four of 14 (29 per cent) following amoxycillin, and three of 11 (27 per cent) after azithromycin . The data illustrate the relationship between resistance to the antimicrobials given to children and their recovery from the middle ear of patients with OME. Rev Prat, 2003 May 1, 53(9), 985 - 8 {Acute laryngeal dyspnea}; Cros AM et al.; Laryngeal dyspnea is a life-threatening emergency situation . The diagnosis is clinical and made from the association of: inspiratory bradypnea, intercostal and sus-sternal inspiratory depression, with or without stridor . The aetiologies are most often laryngeal tumours or inflammatory oedema; incidence of epiglottitis has decreased due to vaccine against Haemophilus influenzae . Airway obstruction due to foreign body includes acute laryngeal dyspnea and reflex paroxysmal coughing without fever . Management of a laryngeal dyspnea depends on the aetiology and the severity of clinical symptoms . Medical treatment associates racemic epinephrine aerosol, steroids, and oxygenation . In the presence of severe dyspnea, intubation after anaesthetising the patient and positive pressure ventilation is required. Respir Med, 2003 Jun, 97(6), 625 - 33 Telithromycin in the treatment of community-acquired pneumonia: a pooled analysis; Hagberg L et al.; The efficacy of telithromycin has been assessed in six Phase III studies involving adults with mild to moderate community-acquired pneumonia (CAP) with a degree of severity compatible with oral therapy . Patients received telithromycin 800 mg once daily for 7-10 days in three open-label studies (n=870) and three randomized, double-blind, comparator-controlled studies (n=503) . Comparator antibacterials were amoxicillin 1000 mg three-times daily, clarithromycin 500 mg twice daily and trovafloxacin 200 mg once daily . Clinical and bacteriological outcomes were assessed 7-14 days post-therapy . Among telithromycin-treated patients, per-protocol clinical cure rates were 93.1 and 91.0% for the open-label and comparative studies, respectively . Telithromycin treatment was as effective as the comparator agents . High eradication and clinical cure rates were observed for infections caused by key pathogens: Streptococcus pneumoniae including isolates resistant to penicillin G and/or erythromycin A (95.4%), Haemophilus influenzae (89.5%) and Moraxella catarrhalis (90%) . Telithromycin was also highly effective in patients with infections caused by atypical and/or intracellular pathogens and those at increased risk of morbidity . Telithromycin was generally well tolerated . Telithromycin 800 mg once daily for 7-10 days offers a convenient and well-tolerated first-line oral therapy for the empirical treatment of mild to moderate CAP. Health Bull (Edinb), 2000 Sep, 58(5), 390 - 5 An audit of the vaccination and antibiotic prophylaxis practices amongst patients splenectomised in Lothian; Pickering J et al.; OBJECTIVE: To evaluate current post-splenectomy immunisation and antibiotic prophylaxis practices amongst patients splenectomised in Lothian between 1st January 1989 and 31st December 1997 . DESIGN: Retrospective cross-sectional study of the general practitioners of patients recorded as having had a splenectomy operation . SETTING: Lothian Health Board (population 771,000) . SUBJECTS: Asplenic patients recorded on Scottish Morbidity Records as having had a splenectomy in Lothian between 1st January 1989 and 31st December 1997 . RESULTS: Eighty point six percent of the patients were vaccinated against Streptococcus pneumoniae, 65.9% were vaccinated against Haemophilus influenzae, and 48.2% were vaccinated against Neisseria meningitidis; 74.8% of patients were being prescribed long-term antibiotic prophylaxis . However, only 37.4% were both vaccinated and prescribed prophylaxis as recommended, in Department of Health guidelines . CONCLUSIONS: The vaccination levels seen in this survey are higher than levels reported in previously published surveys in the UK . Reported rates of post splenectomy vaccination against S . pneumoniae in both the UK and North America in 1993 ranged from 10% to 36% . However, there still remains a substantial proportion of splenectomised patients in Lothian, including some of those with the highest risk of infection, who are not vaccinated or prescribed prophylaxis as recommended. Diagn Microbiol Infect Dis, 2003 Jun, 46(2), 147 - 50 Re-evaluation of quality control guidelines for gatifloxacin and garenoxacin (BMS284756) when susceptibility testing Haemophilus influenzae and Streptococcus pneumoniae; Anderegg TR et al.; An eight laboratory M23-A2 quality control (QC) study was performed for the re-evaluation of gatifloxacin, a new fluoroquinolone, using disk diffusion tests against Streptococcus pneumoniae ATCC 49619 . The study also re-evaluated garenoxacin, a novel investigational des-F(6)-quinolone, using disk diffusion tests against S . pneumoniae ATCC 49619 and broth MIC for Hemophilus influenzae ATCC 49247 . The gatifloxacin zone diameter results for S . pneumoniae did not indicate a need for QC range modification (26-34 mm; 98.3% of results); however, the garenoxacin zone diameters did demonstrate a need for a minor modification (1 mm; 26-34 mm; 96.3% of reported results) . The broth MIC results for H . influenzae showed that 83.1% of the results were at the upper limit of the current range (0.008 microg/ml) published by the National Committee for Clinical Laboratory Standards (NCCLS) . The proposed correction could either be 0.002-0.015 microg/mlor 0.004-0.015 microg/ml, each encompassing 100.0% of reported results (prior and current studies) . All MIC results for control drugs, levofloxacin and moxifloxacin (disks) or gatifloxacin and clarithromycin (MIC), were within published NCCLS ranges. Braz J Infect Dis, 2003 Feb, 7(1), 44 - 61 Antibacterial resistance of community-acquired respiratory tract pathogens recovered from patients in Latin America: results from the PROTEKT surveillance study (1999-2000); Mendes C et al.; PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a global surveillance study established in 1999 to monitor antibacterial resistance of respiratory tract organisms . Thirteen centers from Argentina, Brazil and Mexico participated during 1999-2000; they collected 1806 isolates (Streptococcus pneumoniae 518, Haemophilus influenzae 520, Moraxella catarrhalis 140, Staphylococcus aureus 351, S . pyogenes 277) . Overall, 218 (42.1%) of the S . pneumoniae isolates had reduced susceptibility to penicillin, 79 (15.3%) were penicillin-resistant and 79 (15.3%) were erythromycin-resistant . Mexico had the highest prevalence of penicillin (76.5%) and erythromycin (31.2%) resistance . Of 77 erythromycin-resistant S . pneumoniae tested for resistance genotype, 43 possessed mef(A), 33 possessed erm(B) and 1 possessed both erm(B) and mef(A) mechanism . All S . pneumoniae isolates were fully susceptible to telithromycin, linezolid, teicoplanin and vancomycin . Among H . influenzae isolates, 88 (16.9%) produced beta-lactamase, ranging from 11% (Brazil) to 24.5% (Mexico) . Among M . catarrhalis isolates, 138 (98.6%) produced beta-lactamase . Twenty-four (8.7%) of the S . pyogenes isolates were erythromycin-resistant; resistance being attributable to mefA (n=18), ermTR (n=5) and ermB (n=1) . All H . influenzae, M . catarrhalis and S . pyogenes were fully susceptible to telithromycin . Methicillin resistance was found in 26.5% of the S . aureus isolates (Argentina 15%; Mexico 20%; Brazil 31.3%) . Telithromycin was effective against 97.7% of methicillin-susceptible isolates . PROTEKT confirms that antibacterial resistance is an emerging problem in Latin America . The previously reported high levels of pneumococcal resistance to the beta-lactam and macrolides were exceeded . New agents that do not induce resistance or that exert low selective pressure, e.g . telithromycin, are essential to safeguard future antibacterial efficacy. Commun Dis Intell, 2003, 27 Suppl, S61 - 6 SENTRY Antimicrobial Surveillance Program Asia-Pacific region and South Africa; Bell J et al.; The SENTRY Antimicrobial Surveillance Program was initiated in January 1997 and was designed to monitor the predominant pathogens and antimicrobial resistance for both nosocomial and community-acquired infections globally by using validated, reference-quality identification and susceptibility testing methods performed in a central laboratory . Consecutive bacterial or fungal isolates, deemed clinically significant by local criteria, are forwarded to the local reference laboratory from various study objectives . The major objectives include blood stream infections, community-acquired respiratory tract infections (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis), pneumonias in hospitalised patients, skin and soft tissue infections, and urinary tract isolates from hospitalised patients . In 2001, special objectives were introduced to examine gastroenteritis pathogens and beta-haemolytic streptococcal isolates . Over 22 nations participate in SENTRY surveillance globally . The Women's and Children's Hospital, Adelaide has been the reference centre for the Asia-Pacific region and South Africa since 1998, and three other Australian institutions, from Brisbane, Perth, and Adelaide, are part of the global network . All isolates received from our region are tested against up to 29 antimicrobial agents using custom-made broth microdilution panels . The data generated from SENTRY allows Australia to compare our antimicrobial resistance patterns and trends with our regional neighbours. Otol Neurotol, 2003 May, 24(3), 353 - 7 Detection of Chlamydia pneumoniae in cholesteatoma tissue: any pathogenetic role? Ronchetti F, Ronchetti R, Guglielmi F, Chiappini I, Contini C, Filipo R, Santino I, Cerruto R, Bernardeschi D, Barbara M. BACKGROUND: Acquired cholesteatoma is a complication of chronic otitis media that is usually associated with an intense local inflammatory reaction . Cholesteatoma probably arises from epithelial migration close to an ongoing host inflammatory response attributable to a chronic bacterial infection . Chlamydia pneumoniae is an intracellular microorganism associated with several pathologic conditions originally considered noninflammatory, including asthma, atherosclerosis, and Alzheimer disease . To investigate a possible relationship between C . pneumoniae and the development of cholesteatoma, tissue was studied in three different layers by polymerase chain reaction analysis . The results were compared with those relative to other two common middle-ear pathogens, Mycoplasma pneumoniae and Haemophilus influenzae . METHODS: Cholesteatoma specimens were collected from 32 patients undergoing middle ear surgery . A series of 5 microm-thick specimens were obtained at three different tissue levels, internal (matrix), intermediate (perimatrix), and external (granulation tissue), and processed by polymerase chain reaction for detection of C . pneumoniae, H . influenzae, and M . pneumoniae . Fragmentation and polymerase chain reaction amplification were carried out using two substantially different techniques.RESULTS: C . pneumoniae was detected with either polymerase chain reaction techniques in the internal layers in 16 of the 32 cholesteatomas (50%), associated with a positive finding in the intermediate layer in two cases and in the external layer in one case . Four specimens contained H . influenzae, always in the external layer, whereas none contained M . pneumoniae . CONCLUSIONS: The close relationship between cholesteatoma and C . pneumoniae demonstrated by the findings of this study could suggest a direct cause and effect link between the pathogen action and the clinical manifestations . Otherwise, a facilitated colonization by C . pneumoniae and chronic pathology of the ear could both take origin from a peculiar immunologic background of the host. Vaccine, 2003 Jul 4, 21(23), 3330 - 4 Comparative reactogenicity and parental acceptability of pertussis vaccines administered into the ventrogluteal area and anterolateral thigh in children aged 2, 4, 6 and 18 months; Cook IF et al.; The importance of site of injection of combined pertussis/diphtheria/tetanus vaccines was investigated in two single blind studies.In the pilot study, in which the research instrument was trialed, 283 children aged 2-18 months received whole cell pertussis vaccine (DTPw) by the intramuscular route either into the anterolateral thigh or the ventrogluteal site . In the larger randomised study, 566 children aged 2-18 months were similarly injected with acellular pertussis vaccine (DTPa) . Adverse reactions monitored after 24h showed the same lower rates for both vaccines with ventrogluteal injection compared with anterolateral thigh injection for systemic reactions (irritability (P<0.0001), perceived fever (P<0.0001), persistent crying/screaming (P<0.0001) and local reactions (bruising (P<0.0001) and redness/swelling (P<0.0001)) . The Haemophilus influenzae type b vaccine (HibTITER) given concurrently in the contralateral site to the pertussis vaccine showed the same lower rates in both studies for ventrogluteal injection compared with anterolateral thigh injection for local reactions (redness/swelling both studies (P<0.0001) and bruising DTPw study (P<0.0001) and DTPa study (P<0.0004)).Parental acceptability was greater (P<0.0001) in both studies for ventrogluteal injection compared with anterolateral thigh injection. Eur J Epidemiol, 2003, 18(4), 363 - 7 Invasive Haemophilus influenzae disease: an ecological study of sociodemographic risk factors before and after the introduction of Hib conjugate vaccine; Olowokure B et al.; This study examines the impact of H . influenzae type b (Hib) conjugate vaccine on sociodemographic risk factors for invasive H . influenzae disease in the 2 years before and immediately after the introduction of Hib conjugate vaccine . An ecological study design was used and cases were identified using active surveillance employing several surveillance systems . The study population comprised all children aged < 5 years resident in the West Midlands, an English health region, with laboratory confirmed invasive disease 2 years before (1990-1992) and 2 years after (1992-1994) the introduction of Hib conjugate vaccine . Selected sociodemographic variables derived from the UK census were obtained for all census enumeration districts in the region . Each variable was then ranked and divided into six categories . Linear associations between disease rates and sociodemographic variables were examined . Overall, there was a significant reduction in the incidence of invasive H . influenzae disease . In the pre-conjugate vaccine era there were trends of decreasing disease incidence with increasing child population density (p = 0.012) and total population density (p = 0.0023) . In the post-conjugate vaccine period, total population density (p = 0.0275) remained significant and a trend of increasing disease incidence with increasing population mobility (p = 0.0012) was seen . Although Hib conjugate vaccine has resulted in a dramatic reduction in disease incidence changes in sociodemographic risk factors were identified in the post-conjugate vaccine period, particularly population mobility . Our results may have implications for current and future vaccine strategies. Stat Med, 2003 Jun 30, 22(12), 1989 - 98 Implications of genetic traits on vaccine efficacy; Murthy BN; Literature on genetic screening in the community suggests that people having specific genotypes may either get or protect from infection, for example, malaria, human papilloma virus, and haemophilic influenza, for which vaccines are either already developed or being targeted . In such a situation, the evaluation of the efficacy of vaccine in the community needs to be examined with caution . In this paper, I present a method for the estimation of vaccine efficacy (VE) in the presence of genetic traits/component (theta) and the sample size required to estimate the 95 per cent CI with a given relative width for the estimated vaccine efficacy . Considering true efficacy ranging from 40 to 80 per cent and the possible values of the genetic component (theta) ranging from 0 to 60 per cent, the VE was estimated . The 95 per cent confidence intervals (CI) for the estimated VE for relative widths (R) 1.0 and 0.1 were computed . The sample sizes required for each of the unvaccinated and vaccinated cohorts were computed for estimating the 95 per cent CI for given incidence rates in the unvaccinated (Iu) cohort . In the presence of genetic traits I found that the VE was consistently overestimated . There existed change in the location as well as the asymmetry of the 95 per cent CIs over the point estimate of VE . The sample size required for estimating 95 per cent CI of VE was substantially reduced, resulting in savings . The more the genetic component (theta) affecting disease in the community, the more the savings in sample size . I examined the above estimators for (i) VE, (ii) 95 per cent CI for VE and (iii) sample size required for estimating 95 per cent CI of VE using the real-life data from the Haemophilus influenzae type b vaccine trial conducted in Finland and the global genetic structure of encapsulated H . influenza . Because of escalated VE and large savings in sample size for estimating the 95 per cent CI for VE, I recommend that the design should consider the genetic component that causes/protects from infection/disease for the evaluation of efficacy of vaccine in the field . Mol Gen Mikrobiol Virusol, 2003, (2), 21 - 5 {Multilocus sequence-typing for characterization of Moscow strains of Haemophilus influenzae type b}; Platonov AE et al.; Haemophilius influenzae, type b (Hib) bacteria, were genotyped by multilocus sequence typing (MLST) using 5 loci (adk, fucK, mdh, pgi, recA) . 42 Moscow Hib strains (including 38 isolates form cerebrospinal fluid of children, who had purulent meningitis in 1999-2001, and 4 strains isolated from healthy carriers of Hib), as well as 2 strains from Yekaterinburg were studied . In MLST a strain is characterized, by alleles and their combinations (an allele profile) referred to also as sequence-type (ST) . 9 Sts were identified within the Russian Hib bacteria: ST-1 was found in 25 strains (57%), ST-12 was found in 8 strains (18%), ST-11 was found in 4 strains (9%) and ST-15 was found in 2 strains (4.5%); all other STs strains (13, 14, 16, 17, 51) were found in isolated cases (2.3%) . A comparison of allelic profiles and of nucleotide sequences showed that 93% of Russian isolates, i.e . strain with ST-1, 11, 12, 13, 15 and 17, belong to one and the same clonal complex . 2 isolates from Norway and Sweden from among 7 foreign Hib strains studied up to now can be described as belonging to the same clonal complex; 5 Hib strains were different from the Russian ones. Pediatr Infect Dis J, 2003 Jun, 22(6), 557 - 62 HACEK endocarditis in infants and children: two cases and a literature review; Feder HM Jr et al.; We report 2 cases of Haemophilus parainfluenzae endocarditis and review 34 cases of HACEK endocarditis from the literature . HACEK organisms are the most common cause of Gram-negative endocarditis in children . They have a propensity to form friable vegetations (especially H . parainfluenzae) that break off and cause symptomatic emboli . HACEK endocarditis (from a review of the 36 published cases) may involve previously normal hearts (33%), may be complicated by embolization (31%) and may require vegetectomy or other surgery (31%) . Mortality with HACEK endocarditis was 14% . HACEK organisms may be resistant to penicillins but are susceptible to third generation cephalosporins. Pediatr Infect Dis J, 2003 Jun, 22(6), 509 - 15 Can acute otitis media caused by Haemophilus influenzae be distinguished from that caused by Streptococcus pneumoniae? Leibovitz E, Satran R, Piglansky L, Raiz S, Press J, Leiberman A, Dagan R. BACKGROUND: Previous limited data suggest that acute otitis media (AOM) caused by Streptococcus pneumoniae can present as a more severe disease than that caused by Haemophilus influenzae or Moraxella catarrhalis, as expressed by both tympanic membrane and systemic findings . OBJECTIVES: To evaluate the severity of disease and impact of various pathogens, age, disease history and previous antibiotic therapy in children with AOM by using a comprehensive clinical/otologic score . PATIENTS AND METHODS: The study group consisted of 372 children ages 3 to 36 months with AOM seen at the pediatric emergency room during 1996 through 2001 . All patients had tympanocentesis and middle ear fluid culture performed at enrollment . Clinical status was determined by a clinical/otologic score evaluating severity (0 = absent to 3 = severe) of tympanic membrane findings (redness and bulging) and patient's fever, irritability and ear tugging . Maximal severity score was 15 . RESULTS: There were 138 (37%) H . influenzae, 76 (21%) S . pneumoniae, 64 (17%) mixed infections (H . influenzae + S . pneumoniae) and 94 (25%) culture-negative cases . The overall clinical/otologic score was higher in culture-positive than in culture-negative patients (9.27 +/- 2.75 vs.8.38 +/- 3.08, P = 0.01) . When analyzed by age groups, this difference was significant only for the youngest age group (3 to 6 months, P = 0.05) . The severity scores for AOM caused by H . influenzae and S . pneumoniae were significantly higher than in the culture-negative AOM when tympanic membrane redness and bulging were analyzed separately . No differences were recorded in clinical/otologic scores between different pathogens (9.49 +/- 2.86, 9.03 +/- 2.72 and 9.09 +/- 2.54 for H . influenzae, S . pneumoniae and H . influenzae + S . pneumoniae, respectively) . The mean clinical/otologic score was higher in culture-positive than in culture-negative patients without relationship to previous antibiotic treatment or number of previous AOM episodes . CONCLUSIONS: (1) The clinical/otologic score of culture-positive young infants was higher than that of culture-negative infants; (2) the severity of tympanic membrane redness and bulging were the most indicative factors discriminating between a bacterial and nonbacterial etiology of AOM; and (3) the use of a clinical/otologic score could not discriminate among various bacterial etiologies of AOM. Vaccine, 2003 Jun 20, 21(21-22), 2906 - 10 The immunogenicity of oral poliomyelitis vaccine in a primary vaccination series at 2, 4 and 6 months given concurrently with Hib, hepatitis B and diphtheria, tetanus and whole-cell pertussis vaccines administered as three separate injections or as a combination pentavalent vaccine; Hogg K et al.; The increasing number of infant immunisations has spurred development of novel combination vaccines . This investigation assesses the immunogenicity of oral poliomyelitis vaccine (OPV) under current and possible new conditions, to help ensure vaccination regimes continue to provide optimal protection against polio in the final stages of polio eradication . Neutralising antibody titres were measured in approximately 200 infants immunised with OPV at 2, 4 and 6 months in tandem with either a combined pentavalent liquid Haemophilus influenza B (Hib), hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine or three separate but concurrently administered licensed vaccines (diphtheria, tetanus and whole-cell pertussis (DTP), lyophilised Hib, and hepatitis B) . Following three doses of OPV, at least 98% of infants demonstrated neutralising antibodies at 1:8 to each poliovirus type under both vaccination regimes, and geometric mean titres (GMTs) well above the suggested protective titre were also observed for all poliovirus types . OPV appears to be effective not only in producing protective antibody titres in an extremely high proportion of infants when given in combination with currently licensed vaccines, but also when administered together with the combination pentavalent vaccine under study . This is encouraging for the continued role of OPV in infant immunisation. Infect Genet Evol, 2001 Jul, 1(1), 29 - 39 Dynamics of bacterial colonisation in the respiratory tract of patients with cystic fibrosis; Renders N et al.; Mutations in the human genome may result in altered phenotypes . The cystic fibrosis (CF) patient, for instance, suffers from an aberrant composition of the epithelial lining of the gastrointestinal and respiratory tract . In this particular case, a single point mutation in the cystic fibrosis conductance regulator (CFTR) gene results in major physiological changes resulting in ecological changes that generate a niche particularly attractive to a selected set of microbial pathogens . We here present a review on the dynamics of the bacterial populations inhabiting the CF lung . Studies focusing on Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa will be summarised and discussed, whereas the technology used for microbial characterisation will be shortly highlighted . Emphasis, however, will be on those studies that assessed the genetic diversity among clinical isolates that were obtained over prolonged periods of time, enabling the distinction between persistent colonisation versus frequent re-infection by the selected pathogens . Evolutionary adaptation of pathogens to the CF lung is a common theme in many of these studies. Infect Genet Evol, 2003 May, 3(1), 57 - 66 High rates of recombination in otitis media isolates of non-typeable Haemophilus influenzae; Cody AJ et al.; Non-typeable (NT) or capsule-deficient, Haemophilus influenzae (Hi) is a common commensal of the upper respiratory tract of humans and can be pathogenic resulting in diseases such as otitis media, sinusitis and pneumonia . The lipopolysaccharide (LPS) of NTHi is a major virulence factor that displays substantial intra-strain and inter-strain variation of its oligosaccharide structures . To investigate the genetic basis of LPS variation we sequenced internal regions of each of seven genes required for the biosynthesis of either the inner or the outer core oligosaccharide structures . These sequences were obtained from 25 representative NTHi isolates from episodes of otitis media . We found abundant evidence of recombination among LPS genes of NTHi, a finding in marked contrast to previous analyses of biosynthetic genes for capsular polysaccharide, a well-documented virulence factor of Hi . We found mosaic sequences, linkage equilibrium between loci and a lack of congruence between gene trees . These high rates were not confined to LPS genes since evidence for similar amounts of recombination was also found in eight housekeeping genes in a subset of the same 25 isolates . These findings provide a population based foundation for a better understanding of the role of NTHi LPS as a virulence factor and its potential as a candidate vaccine. Sex Transm Infect, 2003 Jun, 79(3), 202 - 7 Increasing relative prevalence of HSV-2 infection among men with genital ulcers from a mining community in South Africa; Lai W et al.; OBJECTIVES: To determine the aetiology of genital ulcer disease (GUD) and its association with HIV infection in the mining community of Carletonville, South Africa, from two cross sectional surveys of consecutive men presenting with genital lesions during October 1993 to January 1994 and July to November 1998 . METHODS: A multiplex polymerase chain reaction (M-PCR) assay combined with amplicon detection was used to identify DNA specific sequences of Treponema pallidum, herpes simplex virus (HSV), and Haemophilus ducreyi . A real time PCR assay was used to differentiate between HSV-1 and HSV-2 . RESULTS: M-PCR detected T pallidum, HSV, and H ducreyi in 10.3%, 17.2%, and 69.4% of 232 GUD patients during 1993-4 and in 12.4%, 36.0%, and 50.5% of 186 GUD patients in 1998 . The proportion of patients with more than one agent increased significantly from 7.3% (17/232) in 1993-4 to 16.7% (31/186) in 1998 (p <0.01) . HSV-2 was detected in a higher proportion of ulcer specimens from HIV infected patients than in specimens from HIV uninfected patients during both time periods (1993-4: 26.2% v 6.7%, p <0.001; 1998: 42.1% v 29.6%, p >0.09) . CONCLUSIONS: Based on two cross sectional surveys, 4 years apart, chancroid remained the leading cause of GUD in men who presented at the STD clinic with genital ulcers in the mining community of Carletonville, South Africa . The relative prevalence of primary syphilis has remained low . However, HSV-2 has emerged as a more significant cause of GUD and the proportion of GUD patients infected with more than one agent also increased significantly . HSV-2 DNA was detected in a significantly higher proportion of ulcer specimens from HIV positive patients than from HIV negative patients . No association was found between HIV infection status and the relative prevalence of chancroid or syphilis. Pediatr Infect Dis J, 2003 May, 22(5), 405 - 13 Bacteriologic and clinical efficacy of high dose amoxicillin for therapy of acute otitis media in children; Piglansky L et al.; BACKGROUND: High dose (70 to 90 mg/kg/day) amoxicillin is recommended as first line therapy of acute otitis media (AOM) in geographic areas where drug-resistant Streptococcus pneumoniae is prevalent . Information on the bacteriologic efficacy of high dose amoxicillin treatment for AOM is limited . OBJECTIVES: To evaluate the bacteriologic and clinical efficacy of high dose amoxicillin as first line therapy in AOM . METHODS: In a prospective study 50 culture-positive patients ages 3 to 22 months (median, 9 months; 77% <1 year) were treated with high dose amoxicillin (80 mg/kg/day three times a day for 10 days) No antibiotics were administered 72 h before enrollment . Twenty-four (48%) patients presented with their first episode of AOM . Middle ear fluid was cultured by tympanocentesis at enrollment and on Days 4 to 6 of therapy . Additional middle ear fluid cultures were obtained if clinical relapse occurred . Bacteriologic failure was defined by positive cultures on Days 4 to 6 and clinical failure by no change or worsening of AOM signs and symptoms and requirement for additional antibiotics during therapy and/or at end of therapy . Patients were followed until Day 28 +/- 2 . Susceptibility to penicillin and amoxicillin was measured by E-test . RESULTS: Sixty-five organisms were recovered at enrollment: Haemophilus influenzae (38), Streptococcus pneumoniae (24), Streptococcus pyogenes (2) and Moraxella catarrhalis (1) . Eighteen (75%) S . pneumoniae were nonsusceptible to penicillin (MIC > 0.1 microg/ml) . All 24 S . pneumoniae isolates had amoxicillin MIC < or = 2.0 microg/ml . Thirteen (34%) of the 38 H . influenzae were beta-lactamase producers . Eradication was achieved in 41 (82%) patients for 54 of 65 (83%) pathogens: 22 of 24 (92%) S . pneumoniae, 21 of 25 (84%) beta-lactamase-negative H . influenzae, 8 of 13 (62%) beta-lactamase-positive H . influenzae, 2 of 2 S . pyogenes and 1 of 1 M . catarrhalis . Seven organisms not initially present were isolated on Days 4 to 6 in 5 patients: 3 beta-lactamase-positive H . influenzae; 1 beta-lactamase-negative H . influenzae; 2 S . pneumoniae; and 1 M . catarrhalis . In total 14 of 50 (28%) patients failed bacteriologically on Days 4 to 6 (persistence + new infection), of whom 9 (64%) had beta-lactamase-positive H . influenzae . Three (33%) of the 9 patients with bacteriologic failure (2 beta-lactamase-positive H . influenzae, 1 S . pneumoniae) failed also clinically on Days 4 to 6 . CONCLUSIONS: The predominant pathogens isolated from children with AOM failing high dose amoxicillin therapy were beta-lactamase-producing organisms . Because its overall clinical efficacy is good, high dose amoxicillin is still an appropriate choice as first line empiric therapy for AOM, followed by a beta-lactamase-stable drug in the event of failure. Int J Antimicrob Agents, 2003 Jun, 21(6), 581 - 4 The in vitro effects of faropenem on lower respiratory tract pathogens isolated in the United Kingdom; Walsh F et al.; Faropenem is a new oral penem with a structure different from current beta-lactams including carbapenems . The susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis to faropenem, a macrolide, a beta-lactam, a beta-lactam/beta-lactamase inhibitor combination and two fluoroquinolones was investigated . S . pneumoniae was the most susceptible of the three species to faropenem . The MIC(90)s of faropenem against M . catarrhalis and H . influenzae were 0.5 and 1 mg/l, respectively . They were similar to amoxiclav (MIC (90)s of 0.25 and 0.5 mg/l) . The quinolones showed strong activity against H . influenzae . A cluster analysis of the activities of amoxycillin and faropenem demonstrated a direct relationship between the two antimicrobial agent's activities and resistance profiles against both S . pneumoniae and H . influenzae. Int J Antimicrob Agents, 2003 Jun, 21(6), 501 - 9 Resistant Haemophilus influenzae in community-acquired respiratory tract infections: a role for cefixime; Verhoef J et al.; An increase in Haemophilus influenzae resistance has been documented around the world during the last 30 years . Resistance is due to the production of beta-lactamases, and/or changes to penicillin-binding protein (PBP) targets . The resistance problem has led to the need for new therapeutic strategies aimed at maintaining effective management of both upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs) . Among antimicrobial agents tested, third-generation cephalosporins have been shown to possess excellent in vitro activity against beta-lactamase-positive and -negative isolates, corresponding with proven clinical efficacy in a wide range of RTIs . The role of H . influenzae in RTIs is outlined, changing trends in epidemiological surveillance studies monitored and implications for therapy, based upon results of clinical trials discussed. IDrugs, 2003 Mar, 6(3), 240 - 5 The future prospects of oxazolidinones; Johnson AP; The high rates of antimicrobial resistance seen among many Gram-positive pathogens means that there is an ongoing need for new antibacterial drugs . Currently, several pharmaceutical companies are investigating compounds belonging to a new class of anti-Gram-positive agents, the oxazolidinones, one member of which, linezolid, is licensed for clinical use . Interest in oxazolidinones is being stimulated by the results of recent trials demonstrating the excellent clinical efficacy of linezolid in a range of infections . Linezolid is also a relatively safe drug, the main toxicity issue relating to development of thrombocytopenia in some patients receiving prolonged courses . With regard to new oxazolidinones, there is particular interest in analogs that, in early laboratory evaluation, show enhanced activity against the respiratory pathogens Haemophilus influenzae and Moraxella catarrhalis . The future potential of the oxazolidinones will depend on the antibacterial spectra, pharmacokinetic properties and toxicity profiles of new compounds, and the degree to which their clinical use may be affected by the emergence of oxazolidinone-resistant pathogens. Microb Pathog, 2003 Jun, 34(6), 287 - 96 Functional characterization of HgbB, a new hemoglobin binding protein of Pasteurella multocida; Cox AJ et al.; The biological function and role in pathogenesis of a Pasteurella multocida A:1 strain hemoglobin binding protein was investigated . The hgbB gene from the P . multocida A:1 strain, VP161, was cloned and characterized . hgbB was 2991 bp in length and encoded a mature length protein of 111 kDa . HgbB was predicted to be an outer membrane protein and shared 68 and 69% similarity to the hemoglobin/hemoglobin-haptoglobin binding protein, HI0712 from Haemophilus influenzae Rd and HgpC, from H . influenzae b, respectively . HgbB exhibited features typical of TonB dependent receptors, including seven conserved regions typical of these proteins, and conserved invariant residues . Escherichia coli expressing recombinant HgbB was found to bind hemoglobin in a solid phase dot blot binding assay . However, when a truncated form of the protein was expressed in E . coli, cells could no longer bind hemoglobin . Insertional inactivation of hgbB did not affect the ability of P . multocida to bind hemoglobin, nor its ability to produce disease in a mouse model . In addition, recombinant HgbB did not confer any protection against homologous or heterologous challenge. Microb Pathog, 2003 Jun, 34(6), 261 - 5 S-carboxymethylcysteine inhibits the attachment of Streptococcus pneumoniae to human pharyngeal epithelial cells; Cakan G et al.; Streptococcus pneumoniae causes respiratory and other invasive infections . Increased resistance of this bacterium to antibiotics necessitates new approaches to the treatment of infections . Attachment of bacteria to human pharyngeal epithelial cells is the initial step in the pathogenesis of infection and S-carboxymethylcysteine (S-CMC) can modulate the attachment of Moraxella catarrhalis and nontypable Haemophilus influenzae to epithelial cells . Unlike these two, S . pneumoniae is gram-positive and has a well-defined capsule . Here we examined the effects of S-CMC on the attachment and detachment of S . pneumoniae to human pharyngeal epithelial cells in vitro . Treatment of these cells with S-CMC significantly reduced the number of attached S . pneumoniae . S-CMC also resulted in a significant increase in the detachment of already attached S . pneumoniae to epithelial cells . In addition, treatment of S . pneumoniae with S-CMC significantly reduced their ability to attach to epithelial cells, but not the number of viable bacteria . Our study shows that S-CMC modulates the attachment of S . pneumoniae to human pharyngeal epithelial cells by acting both on cells and bacteria. Pediatrics, 2003 Jun, 111(6 Pt 1), e641 - 4 Response to immunization with measles, tetanus, and Haemophilus influenzae type b vaccines in children who have human immunodeficiency virus type 1 infection and are treated with highly active antiretroviral therapy; Melvin AJ et al.; OBJECTIVE: To assess the level of immunity to measles, tetanus, and Haemophilus influenzae type b (Hib) in previously immunized children who have human immunodeficiency virus (HIV) infection and were treated with highly active antiretroviral therapy (HAART) and to determine the response to reimmunization . METHODS: Retrospective review of clinical data from children who have HIV-1 infection and were treated with HAART . Children were included in the analysis when they had a history of immunizations before treatment with HAART; had specific immunoglobulin G levels to tetanus, measles, or Hib measured after starting HAART but before the receipt of additional immunizations; were reimmunized while on HAART; and had postimmunization immunoglobulin G levels available . RESULTS: Nineteen children (median age: 7 years; range: 3-14 years) who were treated with 3 to 5 drug HAART regimens for a median of 20 months (range: 8-37) met the criteria for at least 1 antigen and were included in this review . Fifteen (79%) of the 19 had plasma RNA levels <50 copies/mL . The median CD4% before HAART was 26% (range: 1-41) and at the time of immunization, 35% (range: 20-54) . Before reimmunization, 1 (5%) of 18 children had detectable antibody levels to measles, 6 (35%) of 17 had detectable antibody levels to tetanus, and 14 (78%) of 18 had detectable antibody levels to Hib . After immunization, 15 (83%) of 18, 10 (90%) of 11, and 3 (75%) of 4 seroconverted to measles, tetanus, and Hib, respectively . Antibody levels remained detectable after 1 year in the majority of children tested . CONCLUSIONS: Consideration should be given to readministering childhood immunizations to children who have HIV infection and are treated successfully with combination antiretroviral therapy. EMBO J, 2003 Jun 2, 22(11), 2593 - 603 Crystal structure of tRNA(m1G37)methyltransferase: insights into tRNA recognition; Ahn HJ et al.; tRNA(m(1)G37)methyltransferase (TrmD) catalyzes the transfer of a methyl group from S-adenosyl-L- methionine (AdoMet) to G(37) within a subset of bacterial tRNA species, which have a G residue at the 36th position . The modified guanosine is adjacent to and 3' of the anticodon and is essential for the maintenance of the correct reading frame during translation . Here we report four crystal structures of TrmD from Haemophilus influenzae, as binary complexes with either AdoMet or S-adenosyl-L-homocysteine (AdoHcy), as a ternary complex with AdoHcy and phosphate, and as an apo form . This first structure of TrmD indicates that it functions as a dimer . It also suggests the binding mode of G(36)G(37) in the active site of TrmD and the catalytic mechanism . The N-terminal domain has a trefoil knot, in which AdoMet or AdoHcy is bound in a novel, bent conformation . The C-terminal domain shows structural similarity to trp repressor . We propose a plausible model for the TrmD(2)-tRNA(2) complex, which provides insights into recognition of the general tRNA structure by TrmD. FEMS Immunol Med Microbiol, 2003 Jun 10, 37(1), 69 - 75 Infectious exacerbations of chronic obstructive pulmonary disease associated with respiratory viruses and non-typeable Haemophilus influenzae; Bandi V et al.; Infectious exacerbations of chronic obstructive pulmonary disease (COPD) have been reported to occur with both viral and bacterial pathogens . In this study, 35 exacerbations associated with the isolation of non-typeable Haemophilus influenzae from sputum were identified as part of a prospective longitudinal study . Samples from these patients were subjected to immunoassays to identify a new immune response to the homologous isolate of non-typeable H . influenzae to more accurately assess a bacterial etiology . These patients also were studied carefully for evidence of viral infection using viral culture, serology and polymerase chain reaction-based assays . Sixteen of 35 exacerbations (45.7%) were associated with evidence of acute viral infection and 11 of the 35 exacerbations (31.4%) were associated with the development of new serum IgG to homologous non-typeable H . influenzae . Overall, evidence of infection with a respiratory virus or non-typeable H . influenzae was seen in 24 of 35 exacerbations (68.6%) . No association between viral infection and immune response to non-typeable H . influenzae was observed, although a trend toward an immune response to non-typeable H . influenzae and absence of viral infection was seen . The results show that exacerbations in adults with COPD were associated with infection caused by virus alone, non-typeable H . influenzae alone, or virus and non-typeable H . influenzae simultaneously. Arch Dis Child, 2003 Jun, 88(6), 536 - 9 Chloramphenicol or ceftriaxone, or both, as treatment for meningitis in developing countries? Duke T, Michael A, Mokela D, Wal T, Reeder J. AIMS: To determine in children with meningitis whether there is any difference in mortality and neurological sequelae using chloramphenicol as first line treatment, with a change to ceftriaxone if chloramphenicol resistance is shown in vitro, compared to using ceftriaxone as first line treatment, with a change to chloramphenicol if there is no evidence of in vitro resistance . METHODS: An observational study with a retrospective control group nested within a randomised trial of fluid management for bacterial meningitis where clinical care was standardised . Chloramphenicol is standard treatment for bacterial meningitis in Papua New Guinea . In the first 150 cases we used chloramphenicol and only changed treatment to ceftriaxone if chloramphenicol resistance for cerebrospinal fluid isolates was proved . After finding 20% of Haemophilus influenzae were resistant to chloramphenicol, and that most affected children had poor outcomes, we changed to an alternative strategy . In the next 196 cases first line treatment was ceftriaxone and treatment was changed to chloramphenicol if the isolated bacteria were found to be susceptible . RESULTS: When chloramphenicol was used as first line treatment for meningitis followed by ceftriaxone when in vitro resistance was shown, there was invariably a very poor outcome in chloramphenicol resistant disease (71% of children died or had severe neurological complications) . Using ceftriaxone as first line treatment was effective in reducing mortality and neurological sequelae from chloramphenicol resistant Haemophilus influenzae type (71% v 9%, relative risk 0.13; 95% CI 0.02 to 0.87; p = 0.013) . Changing to chloramphenicol if there was no evidence of in vitro resistance was less than half the cost of empirical use of ceftriaxone for a full course for all children with meningitis . CONCLUSIONS: Using a third generation cephalosporin as first line treatment is effective in dealing with the problem of poor outcomes from meningitis due to Haemophilus influenzae that is resistant to chloramphenicol, and a strategy of changing to chloramphenicol if in vitro susceptibility is shown will reduce the use of expensive third generation cephalosporins without comprising on clinical outcomes . This highlights the urgent need to reduce the costs of third generation cephalosporins, to improve bacteriological services in developing countries, and to introduce effective and affordable vaccines against H influenzae and Streptococcus pneumoniae. N Y State Dent J, 2003 Mar, 69(3), 34 - 6 Haemophilus influenza cellulitis . A review and case report; Branca G et al.; Buccal cellulitis resulting from Haemophilus Influenzae type B (Hlb) is an uncommon yet potentially life-threatening illness that afflicts the facial soft tissues of the very young . Early recognition is essential for the effective treatment of this illness . A clinical case of Haemophilus Influenzae buccal cellulitis is presented, accompanied by a discussion of the presenting symptoms, diagnosis and treatment of this unusual childhood infection. Infect Immun, 2003 Jun, 71(6), 3639 - 44 Complete sequence of the cap locus of Haemophilus influenzae serotype b and nonencapsulated b capsule-negative variants; Satola SW et al.; The complete capsule (cap) loci from three Haemophilus influenzae strains, one serotype b (Hib) and two nonencapsulated b capsule-negative variants, were sequenced . Two new open reading frames, hcsA and hcsB, were identified in region III and thought to be involved in postpolymerization modification of the capsule . The location of the cap locus in the Haemophilus influenzae chromosome was identified within section 97 of the Rd genome (chromosomal coordinates 1074542 to 1086327) and found to be the same for the Hib and two Hib(-) strains as well as some other encapsulated division I H . influenzae strains. Infect Immun, 2003 Jun, 71(6), 3454 - 62 Nontypeable Haemophilus influenzae gene expression induced in vivo in a chinchilla model of otitis media; Mason KM et al.; The gram-negative bacterium nontypeable Haemophilus influenzae (NTHI) is the predominant pathogen in chronic otitis media with effusion and, with Streptococcus pneumoniae and Moraxella catarrhalis, is a causative agent of acute otitis media . To identify potential virulence determinants, bacterial gene expression was monitored by differential fluorescence induction during early disease progression in one specific anatomical niche of a chinchilla model of NTHI-induced otitis media . Genomic DNA fragments from NTHI strain 86-028NP were cloned upstream of the promoterless gfpmut3 gene . NTHI strain 86-028NP served as the host for the promoter trap library . Pools of 2,000 transformants were inoculated into the left and right middle ear cavities of chinchillas . Middle ear effusions were recovered by epitympanic tap at 24 and 48 h, and clones containing promoter elements that were induced in vivo and producing green fluorescent protein were isolated by two-color fluorescence-activated cell sorting . Insert DNA was sequenced and compared to the complete genome sequence of H . influenzae strain Rd . In a screen of 16,000 clones, we have isolated 44 clones that contain unique gene fragments encoding biosynthetic enzymes, metabolic and regulatory proteins, and hypothetical proteins of unknown function . An additional eight clones contain gene fragments unique to our NTHI isolate . Using quantitative reverse transcription-PCR, we have confirmed that 26 clones demonstrated increased gene expression in vivo relative to expression in vitro . These data provide insight into the response of NTHI bacteria as they sense and respond to the middle ear microenvironment during early events of otitis media. Antimicrob Agents Chemother, 2003 Jun, 47(6), 1963 - 7 In vitro activities of telithromycin and 10 oral agents against aerobic and anaerobic pathogens isolated from antral puncture specimens from patients with sinusitis; Goldstein EJ et al.; A study of the comparative in vitro activity of telithromycin, a new ketolide, against 155 aerobic and 171 anaerobic antral sinus puncture isolates showed it to be active against a broad range of sinus pathogens . All pneumococci, including erythromycin-resistant strains, were susceptible to telithromycin at < or = 0.5 microg/ml; all Haemophilus influenzae and Eikenella corrodens strains were inhibited by < or = 4 microg of telithromycin/ml; all Moraxella spp . and beta-lactamase-producing Prevotella species strains were inhibited by < or = 0.25 and 0.5 microg of telithromycin/ml, respectively . Among all anaerobes tested, 94% (160 of 171 strains) were susceptible to < or = 4 microg of telithromycin/ml; however, 8 of 17 (47%) Fusobacterium strains, 2 Veillonella strains, and 1 Peptostreptococcus micros strain required > 4 microg of telithromycin/ml for inhibition . Telithromycin may offer a therapeutic alternative for sinus infections, including those due to erythromycin-resistant pneumococci. Antimicrob Agents Chemother, 2003 Jun, 47(6), 1875 - 81 Antimicrobial resistance in Haemophilus influenzae and Moraxella catarrhalis respiratory tract isolates: results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002; Zhanel GG et al.; A total of 7,566 unique patient isolates of Haemophilus influenzae and 2,314 unique patient isolates of Moraxella catarrhalis were collected between October 1997 and June 2002 from 25 medical centers in 9 of the 10 Canadian provinces . Among the 7,566 H . influenzae isolates, 22.5% produced beta-lactamase, while 92.4% of the 2,314 M . catarrhalis isolates produced beta-lactamase . The incidence of beta-lactamase-producing H . influenzae isolates decreased significantly over the 5-year study period, from 24.2% in 1997-1998 to 18.6% in 2001-2002 (P < 0.01) . The incidence of beta-lactamase-producing M . catarrhalis isolates did not change over the study period . The overall rates of resistance to amoxicillin and amoxicillin-clavulanate for H . influenzae were 19.3 and 0.1%, respectively . The rank order of cephalosporin activity based on the MICs at which 90% of isolates were inhibited (MIC(90)s) was cefotaxime > cefixime > cefuroxime > cefprozil > cefaclor . On the basis of the MICs, azithromycin was more active than clarithromycin (14-OH clarithromycin was not tested); however, on the basis of the NCCLS breakpoints, resistance rates were 2.1 and 1.6%, respectively . Rates of resistance to other agents were as follows: doxycycline, 1.5%; trimethoprim-sulfamethoxazole, 14.2%; and chloramphenicol, 0.2% . All fluoroquinolones tested, including the investigational fluoroquinolones BMS284756 (garenoxacin) and ABT-492, displayed potent activities against H . influenzae, with MIC(90)s of < or = 0.03 microg/ml . The MIC(90)s of the investigational ketolides telithromycin and ABT-773 were 2 and 4 microg/ml, respectively, and the MIC(90) of the investigational glycylcycline GAR-936 (tigecycline) was 4 microg/ml . Among the M . catarrhalis isolates tested, the resistance rates derived by using the NCCLS breakpoint criteria for H . influenzae were <1% for all antibiotics tested except trimethoprim-sulfamethoxazole (1.5%) . In summary, the incidence of beta-lactamase-positive H . influenzae strains in Canada is decreasing (18.6% in 2001-2002), while the incidence of beta-lactamase-positive M . catarrhalis strains has remained constant (90.0% in 2001-2002). Antimicrob Agents Chemother, 2003 Jun, 47(6), 1790 - 7 Susceptibilities to levofloxacin in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis clinical isolates from children: results from 2000-2001 and 2001-2002 TRUST studies in the United States; Karlowsky JA et al.; Among respiratory tract isolates of Streptococcus pneumoniae from children, resistance to penicillins, cephalosporins, macrolides, and trimethoprim-sulfamethoxazole (SXT) increases on an annual basis . Pediatric patients who do not respond to conventional therapy for respiratory tract infections someday may be treated with fluoroquinolones . In this study, MICs of beta-lactams, azithromycin, SXT, and levofloxacin were determined and interpreted by using NCCLS guidelines for isolates of S . pneumoniae (2,834 from children and 10,966 from adults), Haemophilus influenzae (629 from children and 2,281 from adults), and Moraxella catarrhalis (389 from children and 1,357 from adults) collected during the 2000-2001 and 2001-2002 respiratory illness seasons in the United States as part of the ongoing TRUST surveillance studies . Rates of resistance to penicillin, azithromycin, and SXT were > or = 7.5% higher among patients < or = 4 years old than among patients 5 to 10, 11 to 17, and > or = 18 years old in both the 2000-2001 and the 2001-2002 respiratory illness seasons . Levofloxacin resistance was detected in 2 of 2,834 isolates (0.07%) from patients <18 years old . Levofloxacin MICs of 0.25 to 1 micro g/ml accounted for 99.6, 99.5, 99.3, 99.7, 98.4, and 98.0% of isolates from patients < 2, 2 to 4, 5 to 10, 11 to 17, 18 to 64, and > 64 years old . Multidrug resistance was twice as common among patients < or = 4 years old (25.3%) as among patients 5 to 10 years old (13.7%), 11 to 17 years old (11.9%), 18 to 64 years old (12.1%), and > 64 years old (12.4%) . The most common multidrug resistance phenotype in S . pneumoniae isolates for all age groups was resistance to penicillin, azithromycin, and SXT (70.3 to 76.6%) . For H . influenzae and M . catarrhalis isolates from patients < 2, 2 to 4, 5 to 10, 11 to 17, 18 to 64, and > 64 years old, levofloxacin MICs at which 90% of the isolates were inhibited were 0.015 and 0.03 to 0.06 microg/ml, respectively, in the 2000-2001 and 2001-2002 respiratory illness seasons . In the 2000-2001 and 2001-2002 respiratory illness season surveillance studies in the United States, 99.9% of pediatric isolates of S . pneumoniae were susceptible to levofloxacin . If fluoroquinolones become a treatment option for pediatric patients, careful monitoring of fluoroquinolone susceptibilities will be increasingly important in future surveillance studies. Can J Vet Res, 2003 May, 67(2), 146 - 50 Naturally-farrowed, artificially-reared pigs as an alternative model for experimental infection by Haemophilus parasuis; Oliveira S et al.; The use of naturally-farrowed, artificially-reared piglets as an alternative model to study Haemophilus parasuis infections was evaluated . Two trials were performed in order to evaluate the proposed model . In trial 1, animals were vaccinated and challenged with H . parasuis . Results showed that the proposed model was effectively used to evaluate protective immunity against this organism . In trial 2, animals were challenged with different doses of H . parasuis . Results showed that the severity of clinical signs and lesions tended to increase with higher doses . The reproduction of clinical signs and lesions characteristic of H . parasuis systemic infection was successful in both trials, proving that this model is a viable alternative to specific-pathogen free and cesarean-derived, colostrum-deprived pigs. Biochim Biophys Acta, 2003 May 30, 1648(1-2), 203 - 9 The molecular class C acid phosphatase of Chryseobacterium meningosepticum (OlpA) is a broad-spectrum nucleotidase with preferential activity on 5'-nucleotides; Passariello C et al.; The olpA gene of Chryseobacterium meningosepticum, encoding a molecular class C phosphatase, was cloned and expressed in Escherichia coli . The gene encodes a 29-kDa polypeptide containing an amino-terminal signal peptide typical of bacterial membrane lipoproteins . Expression in E . coli results in a functional product that mostly partitions in the outer membrane . A secreted soluble OlpA derivative (sOlpA) lacking the N-terminal cysteine residue for lipid anchoring was produced in E . coli and purified by means of two steps of ion exchange chromatography . Analysis of the kinetic parameters of sOlpA with several organic phosphoesters revealed that the enzyme was able to efficiently hydrolyze nucleotide monophosphates, with a strong preference for 5'-nucleotides and for 3'-AMP . The enzyme was also able to hydrolyze sugar phosphates and beta-glycerol phosphate, although with a lower efficiency, whereas it was apparently inactive against nucleotide di- and triphosphates, diesters, and phytate . OlpA, therefore, can be considered a broad-spectrum nucleotidase with preference for 5'-nucleotides . Its functional behaviour exhibits differences from that of the Haemophilus influenzae OMP P4 lipoprotein, revealing functional heterogeneity among phosphatases of molecular class C. Carbohydr Res, 2003 May 23, 338(11), 1223 - 8 Structural analysis of the lipooligosaccharide from the commensal Haemophilus somnus strain 1P; Cox AD et al.; The structure of the lipooligosaccharide (LOS) from the commensal Haemophilus somnus strain 1P was elucidated . The structure of the O-deacylated LOS was established by monosaccharide analysis, NMR spectroscopy and mass spectrometry . The following structure for the O-deacylated LOS was determined on the basis of the combined data from these experiments . {chemical structure: see text} In the structure Kdo is 3-deoxy-D-manno-octulosonic acid, Hep is L-glycero-D-manno-heptose and lipid A-OH refers to O-deacylated Lipid A . The elucidation of this structure has increased our understanding of the relationship between the variability in LOS structure and the pathogenic potential of this organism . Specifically, the inability of this commensal strain to sialylate its LOS suggests that LOS sialylation could be a crucial virulence factor for H . somnus. Vaccine, 2003 Jun 2, 21(19-20), 2273 - 87 Development and clinical testing of multivalent vaccines based on a diphtheria-tetanus-acellular pertussis vaccine: difficulties encountered and lessons learned; Capiau C et al.; The widespread use of whole-cell pertussis vaccines in the second half of the 20th century have reduced the incidence of the disease significantly . However, in some countries, concerns about the reactogenicity and potential neurological damage associated with whole-cell vaccines led to a decrease in vaccine acceptance and an increase in morbidity and mortality of pertussis in several countries . This prompted the development of less reactogenic acellular pertussis vaccines combined with diphtheria and tetanus toxoids, initially in Japan and later in other countries . In Europe, the improved diphtheria, tetanus and acellular pertussis (DTPa) vaccine was first introduced in March 1994.The pertussis component of this DTPa vaccine, developed by Glaxo SmithKline, consists of pertussis toxoid, filamentous haemagglutinin and pertactin . The vaccine is well tolerated, with a lower incidence of adverse reactions than after administration of whole-cell vaccines.The long-lasting efficacy and effectiveness of DTPa vaccines have been extensively documented and these are now the cornerstone of a large range of combined vaccines including DTPa-hepatitis B (HBV), DTPa-inactivated polio (IPV) and DTPa-HBV-IPV . A lyophilised Haemophilus influenzae type b (Hib) vaccine can be reconstituted with all of these liquid combinations . The introduction of well-tolerated and efficacious DTPa vaccines and their more polyvalent combinations has improved the acceptance and simplified the implementation of childhood immunisation . This paper is a review of the technical and scientific difficulties encountered and the lessons learned over the 10-year period that it took to develop and introduce six multivalent vaccines using the Glaxo SmithKline DTPa as a building block. Diagn Microbiol Infect Dis, 2003 May, 46(1), 55 - 61 Five-year analysis of Haemophilus influenzae isolates with reduced susceptibility to fluoroquinolones: prevalence results from the SENTRY antimicrobial surveillance program; Biedenbach DJ et al.; The appearance of resistance or reduced susceptibility to fluoroquinolones among Hemophilus influenzae has been documented for nearly a decade . Over this time, the use of fluoroquinolones for the treatment of respiratory infections including commonly isolated bacterial causes of community-acquired infections has markedly increased . The documentation of resistance to fluoroquinolones among Streptococcus pneumoniae and H . influenzae has also become more prevalent as measured by peer-reviewed publications . During 1997-2001, a total of 11,355 H . influenzae isolates were tested by reference broth microdilution methods from strains collected by the SENTRY Antimicrobial Surveillance Program (American and European medical centers) . Strains with reduced susceptibility to fluoroquinolones (RSF) were detected during all five study years at an overall rate of 0.15% . Among the tested compounds, sitafloxacin (MIC(50,) 0.03 microg/ml) was the most potent agent against the RSF strains, followed by gemifloxacin (0.12 microg/ml) > garenoxacin = grepafloxacin = levofloxacin = moxifloxacin = trovafloxacin (0.5 microg/ml) > ciprofloxacin = sparfloxacin (1 microg/ml) . Gene sequencing of the quinolone resistance determining region and epidemiologic typing of 30 RSF isolates showed diverse mutational events in gyr A and par C and multiple pulsed-field gel electrophoresis (PFGE) patterns among strains that was not consistent with clonal dissemination . Continued surveillance by global or national networks should continue to monitor for H . influenzae isolates that are refractory to fluoroquinolone therapy. J Microbiol Immunol Infect, 2003 Mar, 36(1), 69 - 71 Acute epiglottitis caused by Haemophilus influenzae type b: a case report; Jiang JH et al.; Acute epiglottitis is an inflammatory, edematous disease of the epiglottis and adjacent structures, usually caused by Haemophilus influenzae type b . It is a life-threatening condition, occurring mainly in childhood . There have never been any reports of this condition in Taiwan . We report a case of 4-year-old boy who presented with characteristics of systemic illness combined with respiratory distress on arrival at the emergency room . His mouth was open and his neck was hyperextended . The diagnosis of epiglottitis was established on the basis of physical examination, lateral neck x-ray, and the finding of an enlarged, swollen, erythematous epiglottis on flexible fiberoptic laryngoscopy . Urine latex agglutination test for H . influenzae type b was positive and a blood culture grew H . influenzae type b . He was treated with cefotaxime and did not require intubation. J Microbiol Immunol Infect, 2003 Mar, 36(1), 41 - 6 Septic arthritis in children: relationship of causative pathogens, complications, and outcome; Wang CL et al.; This retrospective study investigated the causative pathogens, complications, and outcome of 58 children who were hospitalized for septic arthritis at a tertiary care hospital in southern Taiwan from July 1988 to December 2000 . The mean age was 3 years (range, 12 days-16 years) . The males/females ratio was 1.2:1 . Ninety percent of the cases involved lower extremities (knee, hip, and ankle) with the hip being the most common site of infection (54%) . Joint pain (81%) was the most common clinical presentation, followed by fever (74%), local warmness and swelling (72%), and limitation of motion (64%) . Erythrocyte sedimentation rate was elevated (> or = 20 mm/h) initially in 89% of the cases . The predominant causative organism was Staphylococcus aureus (43%, 25/58), 6 isolates of which were methicillin-resistant, followed by coagulase-negative Streptococcus (6), Streptococcus pneumoniae (3), Salmonella spp . (3), Haemophilus influenzae type b (2), and group B Streptococcus (2) . The concomitant complications of septic arthritis were sepsis (9%, 5/58) and meningitis (2%, 1/58) . Ten patients had sequelae, including limitation of motion (6), limping gait (2), limb-length discrepancy (1), and abnormalities of bone growth (1) . This study found that S . aureus was the most common infecting microorganism in septic arthritis in children . Septic arthritis with concomitant osteomyelitis and infection due to methicillin-resistant S . aureus was associated with a significantly increased risk of sequelae (relative risk, 46.4, 95% CI, 2.9-748.8; relative risk, 16 . 2, 95% CI, 1.3-204.9, respectively). Lancet, 2003 May 3, 361(9368), 1523 - 4 Antibody to Haemophilus influenzae type b after routine and catch-up vaccination; Trotter CL et al.; Since 1999, the number of cases of Haemophilus influenzae type b (Hib) disease in the UK has risen . We investigated the role of population immunity in this change by testing more than 2600 serum samples from children aged 1-15 years . After the introduction of the routine Hib conjugate vaccination programme for infants, median antibody titres rose significantly in 1-year-olds . Individuals who received their first dose of vaccine at age 1-4 years in the original catch-up campaign initially had much higher concentrations of antibody than those who had been immunised in infancy . A second catch-up campaign in children aged 6 months to 4 years should be highly effective in boosting immunity and reducing disease in the short term. Lancet, 2003 May 3, 361(9368), 1521 - 3 Risk of vaccine failure after Haemophilus influenzae type b (Hib) combination vaccines with acellular pertussis; McVernon J et al.; An increase in invasive Hib disease incidence in the UK has coincided with the distribution of combination vaccines that contain acellular pertussis (DTaP-Hib) . These vaccines have been associated with reduced immunogenicity of the Hib component, although there is little agreement on the clinical relevance of this finding . We retrospectively compared vaccine formulations given to fully vaccinated Hib cases with those administered to fully immunised age-matched controls using conditional logistic regression . More cases than controls received all three doses of their infant primary course as DTaP-Hib, compared with two or three doses of another Hib vaccine (conditional odds ratio 6.77 {95% CI 3.26-14.07}). Commun Dis Public Health, 2003 Apr, 6(1), 55 - 8 Rising incidence of Haemophilus influenzae type b disease in England and Wales indicates a need for a second catch-up vaccination campaign; Trotter CL et al.; The incidence of invasive Haemophilus influenzae type b (Hib) disease in the UK fell rapidly following the introduction of routine vaccination in 1992 and the implementation of a catch-up campaign in children under 4 years old in 1992-93 . However, since 1999 the number of cases of Hib has been increasing, and in 2002 there were 134 cases in 0-4 year olds (266 in all ages) . While still much less than the prevaccine burden of disease (over 800 cases a year in 0-4 year olds), this increase in incidence is worrying and has sparked a range of detailed investigations . In February 2003, the Department of Health announced a second catch-up campaign offering all children between 6 months and 4 years a further dose of Hib vaccine . The epidemiology of Hib disease in England and Wales between 1990 and 2002 is reviewed here to provide a context for this public health response. J Clin Microbiol, 2003 May, 41(5), 2080 - 3 Pgi genotyping is a surrogate for serotyping of encapsulated Haemophilus influenzae; Anyanwu JN et al.; Study of the epidemiology of invasive infections caused by encapsulated Haemophilus influenzae has been complicated by the poor sensitivity and specificity of the serologic assays used to identify specific capsular polysaccharides . The population structure of these bacteria is highly clonal, however, and serotype is highly correlated with other genetic characteristics . We sought to determine if alleles of the highly conserved phosphoglucose isomerase (pgi) gene correspond to the serotypes of encapsulated H . influenzae strains . pgi alleles of 52 well-characterized encapsulated H . influenzae isolates were amplified by PCR, sequenced, and compared to one another and to additional previously reported H . influenzae pgi alleles . Overall, 83% of the strains possessed pgi alleles associated with the major serotype a, b, e, and f clonotypes that cause the most invasive disease in the United States . Six strains (four type a and two type f) had unusual pgi alleles, which suggested that these strains belonged to less common clonotypes of encapsulated bacteria or were actually nontypeable strains . pgi genotyping may provide a simple and stable surrogate for capsular serotyping . Further studies correlating pgi typing with the expression of capsule are likely to increase our understanding of the epidemiology and pathogenesis of these infections. J Biol Chem, 2003 Jul 25, 278(30), 27811 - 9 Epub 2003 May 06. Transforming growth factor-beta-Smad signaling pathway negatively regulates nontypeable Haemophilus influenzae-induced MUC5AC mucin transcription via mitogen-activated protein kinase (MAPK) phosphatase-1-dependent inhibition of p38 MAPK; Jono H et al.; In contrast to the extensive studies on the role of transforming growth factor-beta (TGF-beta) in regulating cell proliferation, differentiation, and apoptosis over the past decade, relatively little is known about the exact role of TGF-beta signaling in regulating host response in infectious diseases . Most of the recent studies have suggested that TGF-beta inhibits macrophage activation during infections with pathogens such as Trypanosoma cruzi and Leishmania, thereby favoring virulence . In certain situations, however, there is also evidence that TGF-beta has been correlated with enhanced resistance to microbes such as Candida albicans, thus benefiting the host . Despite these distinct observations that mainly focused on macrophages, little is known about how TGF-beta regulates host primary innate defensive responses, such as up-regulation of mucin, in the airway epithelial cells . Moreover, how the TGF-beta-Smad signaling pathway negatively regulates p38 mitogen-activated protein kinase (MAPK), a key pathway mediating host response to bacteria, still remains largely unknown . Here we show that nontypeable Haemophilus influenzae, a major human bacterial pathogen of otitis media and chronic obstructive pulmonary diseases, strongly induces up-regulation of MUC5AC mucin via activation of the Toll-like receptor 2-MyD88-dependent p38 path-way . Activation of TGF-beta-Smad signaling, however, leads to down-regulation of p38 by inducing MAPK phophatase-1, thereby acting as a negative regulator for MUC5AC induction . These studies may bring new insights into the novel role of TGF-beta signaling in attenuating host primary innate defensive responses and enhance our understanding of the signaling mechanism underlying the cross-talk between TGF-beta-Smad signaling pathway and the p38 MAPK pathway. Diagn Microbiol Infect Dis, 2003 Apr, 45(4), 279 - 85 Pathogen of occurrence and susceptibility patterns associated with pneumonia in hospitalized patients in North America: results of the SENTRY Antimicrobial Surveillance Study (2000); Hoban DJ et al.; Antimicrobial selection for patients diagnosed with pneumonia is a major therapeutic challenge and dilemma to the clinical practitioner . In the community setting, patients usually receive empiric oral therapy based upon multiple patient risk factors and locally prevalent pathogen susceptibilities . For patients admitted to the hospital with pneumonia, or who acquire pneumonia while in the hospital, therapy can be initially empiric and then become directed once culture and susceptibility results are known . The SENTRY Antimicrobial Surveillance Program since 1997, has monitored pathogen frequency and antimicrobial susceptibilities in hospitalized patients with pneumonia in North America . In this Study 2,712 pathogens were studied from 30 medical centers (25 in the United States and 5 in Canada) . Over 30 species of organisms were recovered with Staphylococcus aureus comprising 28.0% of all isolates and with four other species (Pseudomonas aeruginosa 20.0%, Streptococcus pneumoniae 9.1%, Klebsiella spp . 7.5% and Haemophilus influenzae 7.3%) constituted 71.9% of isolates submitted . Methicillin (oxacillin)-resistant S . aureus accounted for 43.7% of all S . aureus isolates . Antimicrobials demonstrating significant (>80%) activity against S . aureus were: chloramphenicol (81.6%), tetracycline (91.4%), rifampin (96.4%) and quinupristin/dalfopristin (99.7%); and no isolate was resistant to glycopeptides or linezolid . North American isolates of P . aeruginosa were most susceptible to amikacin (93.7%) > tobramycin (90.2%) > meropenem (89.1%) > imipenem = piperacillin/tazobactam (85.6%) > piperacillin (82.1%) > cefepime (80.5%) . Overall, 32.1% of S . pneumoniae were penicillin non-susceptible while erythromycin susceptibility was only 74.8% . Fluoroquinolones and recent generation cephalosporins retained excellent activity (gatifloxacin {99.2%} > levofloxacin = cefepime {98.8%} > ceftriaxone {97.2%}) against S . pneumoniae . Klebsiella spp . were 100.0% susceptible to the carbapenems (meropenem and imipenem) but extended spectrum beta-lactamases were detected at a rate of 5.4% . The beta-lactamase-positive rate in H . influenzae was 28.6% in North America (71.4% ampicillin-susceptible) . The SENTRY Antimicrobial Surveillance Program continues to identify important North American patterns of pathogen frequency and resistance . Additionally, the provision of multi-year longitudinal data and associated reports allow for comparisons, which function as critical tools for effective patient management and antimicrobial interventions. Pediatrics, 2003 May, 111(5 Pt 1), 925 - 32 Physician knowledge of catch-up regimens and contraindications for childhood immunizations; Cohen NJ et al.; OBJECTIVES: To determine physician success at designing catch-up regimens for children delayed in immunizations and physician knowledge regarding contraindications to immunization . METHODS: A self-administered survey was completed by pediatricians, general practitioners, and family practitioners in Cook County, Illinois . Surveys included 6 open-ended vignettes describing hypothetical children delayed in immunization for whom participants were asked to design catch-up regimens . Bivariate and multivariate logistic regression were used to determine predictors of correct response . The surveys also inquired about management of scenarios that might be perceived as contraindications to immunize with the Haemophilus influenzae type b or measles-mumps-rubella vaccines . RESULTS: The mean score of correct responses was 1.83 of a possible 6.0 . Almost one third of respondents answered all 6 vignettes incorrectly . The proportion of incorrect responses was high for all 6 vignettes (39%-86%), but higher for questions that addressed the immunization of children older than 12 months . Errors in vaccine administration were most commonly attributed to omitted vaccines, with varicella-zoster vaccine and pneumococcal conjugate vaccine omitted most frequently . Pediatricians were >4 times more likely to answer correctly than were family practitioners . Participants in the Vaccines for Children (VFC) program were more than twice as likely to answer correctly than were non-VFC providers . Knowledge of contraindications was inconsistent, particularly for measles-mumps-rubella vaccine . CONCLUSIONS: Childhood vaccine providers have substantial knowledge deficits of recommended immunization schedules and vaccine contraindications that may contribute to missed opportunities to immunize . Pediatricians and participants in the VFC program were more successful at designing catch-up regimens for children with immunization delay. Commun Dis Intell, 2003, 27(1), 1 - 78 Australia's notifiable diseases status, 2001: annual report of the National Notifiable Diseases Surveillance System; Blumer C et al.; In 2001 there were 104,187 notifications of communicable diseases in Australia reported to the National Notifiable Diseases Surveillance System (NNDSS) . The number of notifications in 2001 was an increase of 16 per cent of those reported in 2000 (89,740) and the largest annual total since the NNDSS commenced in 1991 . In 2001, nine new diseases were added to the list of diseases reported to NNDSS and four diseases were removed . The new diseases were cryptosporidiosis, laboratory-confirmed influenza, invasive pneumococcal disease, Japanese encephalitis, Kunjin virus infection, Murray Valley encephalitis virus infection, anthrax, Australian bat lyssavirus, and other lyssaviruses (not elsewhere classified) . Bloodborne virus infections remained the most frequently notified disease (29,057 reports, 27.9% of total), followed by sexually transmitted infections (27,647, 26.5%), gastrointestinal diseases (26,086, 25%), vaccine preventable diseases (13,030 (12.5%), vectorborne diseases (5,294, 5.1%), other bacterial infections (1,978, 1.9%), zoonotic infections (1,091, 1%) and four cases of quarantinable diseases . In 2001 there were increases in the number of notifications of incident hepatitis C, chlamydial infections, pertussis, Barmah Forest virus infection and ornithosis . There were decreases in the number of notifications of hepatitis A, Haemophilus influenzae type b infections, measles, rubella, Ross River virus infections and brucellosis . This report also summarises data on communicable diseases from other surveillance systems including the Laboratory Virology and Serology Reporting Scheme and sentinel general practitioner schemes . In addition, this report comments on other important developments in communicable disease control in Australia in 2001. Nihon Kokyuki Gakkai Zasshi, 2003 Feb, 41(2), 89 - 94