Fiona M. Russell

First Report of Putative Streptococcus pneumoniae Serotype 6D among Nasopharyngeal Isolates from Fijian Children

BACKGROUND A putative Streptococcus pneumoniae serotype, 6D, resulting from the introduction of wciN(beta) into serotype 6B has been proposed. METHODS We studied 98 unique serogroup 6 isolates from Fijian children, two-thirds of whom had received at least 1 dose of 7-valent pneumococcal conjugate vaccine, and 51 invasive isolates from Australian children. We used a polymerase chain reaction (PCR) system that targets both wciN(beta) and the single-nucleotide polymorphism that differentiates serotypes 6A and 6B-wciP584g (6A) and wciP584a (6B). RESULTS Two (9%) of 22 Australian isolates and 24 (38%) of 64 Fijian isolates previously identified as 6A by the Quellung reaction and wciP584g PCR contained wciN(beta) and were designated as 6C; 14 (41%) of 34 Fijian isolates previously identified as 6B by the Quellung reaction and wciP584a PCR contained wciN(beta) and were designated as the new putative serotype 6D. A significantly smaller proportion of children from whom serotype 6D was isolated (2/14 [14%]) had not received PCV-7, compared with the proportion of those from whom serotype 6B was isolated (11/20 [55%]) (P < .05). CONCLUSION This is the first report of naturally occurring S. pneumoniae serotype 6D.

Hyporesponsiveness to re-challenge dose following pneumococcal polysaccharide vaccine at 12 months of age, a randomized controlled trial.

BACKGROUND To evaluate the immunological impact of the 23-valent pneumococcal polysaccharide vaccine (23vPPS) at 12 months, for children who have received zero to three infant doses of seven-valent pneumococcal conjugate vaccine (PCV), on responses to a subsequent exposure to a small dose of 23vPPS (mPPS). METHODS Five hundred and fifty-two Fijian infants were stratified by ethnicity and randomized into eight groups to receive zero, one, two, or three PCV doses at 14 weeks, six and 14 weeks, or six, ten, and 14 weeks. Within each group, half received 23vPPS at 12 months and all received mPPS at 17 months. Sera were taken prior and one month post-mPPS. FINDINGS By 17 months, geometric mean antibody concentrations (GMC) to all 23 serotypes in 23vPPS were significantly higher in children who had received 23vPPS at 12 months compared to those who had not. Post-mPPS, children who had not received the 12 month 23vPPS had a significantly higher GMC for all PCV serotypes compared with those who had (each p<0.02). For the non-PCV serotypes, children who had not received the 12 month 23vPPS had significantly higher GMC for six of 16 non-PCV serotypes (7F, 9N, 12F, 19A, 22F, 33F) than those who did (each p<0.02). After adjusting for the pre-mPPS level, exposure to 23vPPS was associated with a lower response to mPPS for all serotypes (each p<0.001). INTERPRETATION Despite higher antibody concentrations at 17 months in children who had received 23vPPS at 12 months, the response to a re-challenge was poor for all 23 serotypes compared to children who had not received the 12 month 23vPPS.

Evidence on the use of paracetamol in febrile children

Antipyretics, including acetaminophen (paracetamol), are prescribed commonly in children with pyrexia, despite minimal evidence of a clinical benefit. A literature review was performed by searching Medline and the Cochrane databases for research papers on the efficacy of paracetamol in febrile illnesses in children and adverse outcomes related to the use of paracetamol. No studies showed any clear benefit for the use of paracetamol in therapeutic doses in febrile children with viral or bacterial infections or with malaria. Some studies suggested that fever may have a beneficial role in infection, although no definitive prospective studies in children have been done to prove this. The use of paracetamol in therapeutic doses generally is safe, although hepatotoxicity has occurred with recommended dosages in children. In developing countries where malnutrition is common, data on the safety of paracetamol are lacking. The cost of paracetamol for poor families is substantial. No evidence shows that it is beneficial to treat febrile children with paracetamol. Treatment should be given only to children who are in obvious discomfort and those with conditions known to be painful. The role of paracetamol in children with severe malaria or sepsis and in malnourished, febrile children needs to be clarified.

Immunogenicity following one, two, or three doses of the 7-valent pneumococcal conjugate vaccine.

The aim was to identify an appropriate infant pneumococcal vaccination strategy for resource poor countries. Fijian infants received zero, one, two, or three doses of 7-valent pneumococcal conjugate vaccine (PCV) in early infancy. Following three PCV doses, geometric mean concentration (GMC) to all seven serotypes were > or = 1.0 microg/mL, and >85% of children achieved antibody levels > or = 0.35 microg/mL at 18 weeks. Following two doses, GMC were lower for 6B, 14, and 23F, but higher for 19F compared with three doses. Following a single dose, significant responses were seen for all serotypes post-primary series compared with the unvaccinated. By 12 months, differences between two and three doses persisted for serotype 14 only. Although GMC following three doses are higher than after two doses, the differences were small. A single dose may offer some protection for most serotypes.

Pneumococcal Nasopharyngeal Carriage following Reduced Doses of a 7-Valent Pneumococcal Conjugate Vaccine and a 23-Valent Pneumococcal Polysaccharide Vaccine Booster

ABSTRACT This study was conducted to evaluate the effect of a reduced-dose 7-valent pneumococcal conjugate vaccine (PCV) primary series followed by a 23-valent pneumococcal polysaccharide vaccine (23vPPS) booster on nasopharyngeal (NP) pneumococcal carriage. For this purpose, Fijian infants aged 6 weeks were randomized to receive 0, 1, 2, or 3 PCV doses. Within each group, half received 23vPPS at 12 months. NP swabs were taken at 6, 9, 12, and 17 months and were cultured for Streptococcus pneumoniae. Isolates were serotyped by multiplex PCR and a reverse line blot assay. There were no significant differences in PCV vaccine type (VT) carriage between the 3- and 2-dose groups at 12 months. NP VT carriage was significantly higher (P, <0.01) in the unvaccinated group than in the 3-dose group at the age of 9 months. There appeared to be a PCV dose effect in the cumulative proportion of infants carrying the VT, with less VT carriage occurring with more doses of PCV. Non-PCV serotype (NVT) carriage rates were similar for all PCV groups. When groups were pooled by receipt or nonreceipt of 23vPPS at 12 months, there were no differences in pneumococcal, VT, or NVT carriage rates between the 2 groups at the age of 17 months. In conclusion, there appeared to be a PCV dose effect on VT carriage, with less VT carriage occurring with more doses of PCV. By the age of 17 months, NVT carriage rates were similar for all groups. 23vPPS had no impact on carriage, despite the substantial boosts in antibody levels.

Infants aged 12 months can mount adequate serotype-specific IgG responses to pneumococcal polysaccharide vaccine

1 0.17 (0.13-0.22) 2.04 (1.49-2.80) <.0001 2 0.28 (0.23-0.35) 12.48 (9.66-16.12) <.0001 3 0.37 (0.26-0.53) 13.74 (10.55-17.91) <.0001 4 0.08 (0.06-0.10) 2.37 (1.76-3.20) <.0001 5 0.26 (0.20-0.34) 2.77 (2.15-3.57) <.0001 6B 0.14 (0.12-0.17) 0.31 (0.23-0.42) <.05 7F 0.10 (0.08-0.14) 2.58 (1.98-3.37) <.0001 8 0.26 (0.20-0.32) 13.59 (10.72-17.23) <.0001 9N 0.12 (0.09-0.15) 3.06 (2.18-4.30) <.0001 9V 0.09 (0.07-0.12) 1.21 (0.90-1.62) <.0001 10A 0.20 (0.16-0.24) 0.87 (0.65-1.17) <.0001 11A 0.10 (0.08-0.13) 2.21 (1.58-3.08) <.0001 12F 0.06 (0.05-0.08) 0.39 (0.28-0.54) <.0001 14 0.20 (0.16-0.25) 0.41 (0.29-0.59) NS 15B 0.17 (0.14-0.22) 0.79 (0.59-1.05) <.0001 17F 0.11 (0.09-0.13) 1.39 (0.98-1.97) <.0001 18C 0.07 (0.05-0.08) 1.23 (0.88-1.72) <.0001 19A 0.29 (0.24-0.36) 0.79 (0.55-1.12) <.05 19F 0.47 (0.36-0.62) 1.15 (0.81-1.62) NS 20 0.10 (0.08-0.12) 0.90 (0.61-1.34) <.0001 22F 0.36 (0.29-0.46) 5.23 (3.47-7.88) <.0001 23F 0.19 (0.15-0.25) 0.42 (0.30-0.57) NS 33F 0.14 (0.11-0.17) 2.01 (1.44-2.80) <.0001

Severe Bordetella holmesii Infection in a Previously Healthy Adolescent Confirmed by Gene Sequence Analysis

We describe an immunocompetent adolescent who presented with exceptionally severe Bordetella holmesii infection, including previously undescribed manifestations. Sequelae included a severe restrictive lung defect due to pulmonary fibrosis.

Effect of Pneumococcal Vaccination on Nasopharyngeal Carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in Fijian Children

ABSTRACT The 7-valent pneumococcal conjugate vaccine (PCV7) reduces carriage of vaccine type Streptococcus pneumoniae but leads to replacement by nonvaccine serotypes and may affect carriage of other respiratory pathogens. We investigated nasopharyngeal carriage of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in Fijian infants participating in a pneumococcal vaccine trial using quantitative PCR. Vaccination did not affect pathogen carriage rates or densities, whereas significant differences between the two major ethnic groups were observed.

High burden of invasive β-haemolytic streptococcal infections in Fiji

We undertook a 5-year retrospective study of group A streptococcal (GAS) bacteraemia in Fiji, supplemented by a 9-month detailed retrospective study of β-haemolytic streptococcal (BHS) infections. The all-age incidence of GAS bacteraemia over 5 years was 11.6/100 000. Indigenous Fijians were 4.7 times more likely to present with invasive BHS disease than people of other ethnicities, and 6.4 times more likely than Indo-Fijians. The case-fatality rate for invasive BHS infections was 28%. emm-typing was performed on 23 isolates: 17 different emm-types were found, and the emm-type profile was different from that found in industrialized nations. These data support the contentions that elevated rates of invasive BHS and GAS infections are widespread in developing countries, and that the profile of invasive organisms in these settings reflects a wide diversity of emm-types and a paucity of types typically found in industrialized countries.

As a bacterial culture medium, citrated sheep blood agar is a practical alternative to citrated human blood agar in laboratories of developing countries.

ABSTRACT Human blood agar (HuBA) is widely used in developing countries for the isolation of bacteria from clinical specimens. This study compared citrated sheep blood agar (CSBA) and HuBA with defibrinated horse blood agar and defibrinated sheep blood agar (DSBA) for the isolation and antibiotic susceptibility testing of reference and clinical strains of Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus. Reference and clinical strains of all organisms were diluted in brain heart infusion and a clinical specimen of cerebrospinal fluid and cultured on all agars. Viable counts, colony morphology, and colony size were recorded. Susceptibility testing for S. pneumoniae and S. pyogenes was performed on defibrinated sheep blood Mueller-Hinton agar, citrated sheep blood Mueller-Hinton agar (CSB MHA), and human blood Mueller-Hinton agar plates. For all organisms, the colony numbers were similar on all agars. Substantially smaller colony sizes and absent or minimal hemolysis were noted on HuBA for all organisms. Antibiotic susceptibility results for S. pneumoniae were similar for the two sheep blood agars; however, larger zone sizes were displayed on HuBA, and quality control for the reference strain failed on HuBA. For S. pyogenes, larger zone sizes were demonstrated on HuBA and CSBA than on DSBA. Poor hemolysis made interpretation of the zone sizes difficult on HuBA. CSBA is an acceptable alternative for the isolation of these organisms. The characteristic morphology is not evident, and hemolysis is poor on HuBA; and so HuBA is not recommended for use for the isolation or the susceptibility testing of any of these organisms. CSB MHA may be suitable for use for the susceptibility testing of S. pneumoniae.