Serotype-specific avidity is achieved following a single dose of the 7-valent pneumococcal conjugate vaccine, and is enhanced by 23-valent pneumococcal polysaccharide booster at 12 months.

AIM: To evaluate whether the avidity of serotype-specific IgG to pneumococcal serotypes is enhanced by an increased number of doses of the 7-valent pneumococcal conjugate vaccine (PCV) in infancy or by a 12 month 23-valent pneumococcal polysaccharide vaccine (23vPPS) booster, and/or subsequent re-exposure to a small dose of pneumococcal polysaccharide antigens (mPPS) at 17 months. METHODS: Fijian infants aged 6 weeks were recruited, stratified by ethnicity and randomized to 8 groups to receive 0, 1, 2, or 3 doses of PCV, with or without 23vPPS at 12 months. All children received mPPS at 17 months of age. Avidity of serotype-specific IgG for PCV serotypes in the first 12 months and for all 23vPPS serotypes thereafter was assessed by EIA after sodium thiocyanate elution. RESULTS: At one month post primary series, the 2 and 3 PCV dose groups demonstrated similar avidity, with the single dose group tending to have lower avidity. However, by age 9 months, the single dose group had similar avidity to the 2 and 3 PCV groups for most serotypes. The 23vPPS booster enhanced affinity maturation for most serotypes and this was most marked in those groups that received a single PCV dose. There was little further increase following the mPPS. CONCLUSIONS: By 9 months of age, similar avidity can be induced following one, 2 or 3 doses of PCV. A 23vPPS booster at 12 months enhanced affinity maturation with an increase in antibody avidity for most serotypes. Subsequent re-challenge with mPPS at 17 months did not further enhance the avidity of serotype-specific response in the 12 month 23vPPS groups.

Opsonophagocytic activity following a reduced dose 7-valent pneumococcal conjugate vaccine infant primary series and 23-valent pneumococcal polysaccharide vaccine at 12 months of age.

Opsonophagocytic activity (OPA) was measured following reduced infant doses of 7-valent pneumococcal conjugate vaccine (PCV-7) with or without 23-valent pneumococcal polysaccharide vaccine (PPV-23) at 12 months, and subsequent re-exposure to a small dose of pneumococcal polysaccharide antigens (mPPS) at 17 months. Fijian infants were randomized to receive 0, 1, 2, or 3 PCV-7 doses. Half received PPV-23 at 12 months and all received mPPS at 17 months. OPA was performed on up to 14 serotypes. Three and 2 PCV-7 doses resulted in similar OPA for most PCV-7 serotypes up to 9 months and for half of the serotypes at 12 months. A single dose improved OPA compared with the unvaccinated group. PPV-23 significantly improved OPA for all serotypes tested but in general, was associated with diminished responses following re-challenge.

Pneumococcal nasopharyngeal carriage following reduced doses of a 7-valent pneumococcal conjugate vaccine and a 23-valent pneumococcal polysaccharide vaccine booster.

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.

Safety and immunogenicity of the 23-valent pneumococcal polysaccharide vaccine at 12 months of age, following one, two, or three doses of the 7-valent pneumococcal conjugate vaccine in infancy.

Fijian infants aged 6 weeks were stratified by ethnicity and randomized to receive 0, 1, 2, or 3 PCV-7 doses with or without the 23-valent pneumococcal polysaccharide vaccine (PPV-23) at 12 months. Strong booster effects for all 7 PCV-7 serotypes were elicited, and for 4/7 serotypes these responses were highest in the single PCV-7 group. There were fourfold rises in GMC for all non-PCV-7 serotypes. By 17 months the PPV-23 group still had significantly higher GMC (each p<0.001) for all serotypes. The PPV-23 was well tolerated and induced excellent responses for all serotypes which were greatest in the single PCV-7 group.

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.

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.

Risk factors for symptoms of childhood asthma, allergic rhinoconjunctivitis and eczema in the Pacific: an ISAAC Phase III study.

BACKGROUND AND METHODS: Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC) was conducted in eight Pacific countries, five of which (Samoa, Fiji, Tokelau, French Polynesia and New Caledonia) collected environmental questionnaire (EQ) data. We report the findings of the EQ analyses below. RESULTS: The major factors associated with current wheeze were regular margarine consumption (prevalence odds ratio [POR] 1.19, 95%CI 1.01-1.40), paracetamol use (POR 1.35, 95%CI 1.11-1.64), electric cooking (POR 1.42, 95%CI 1.11-1.80), regular exercise (POR 1.44, 95%CI 1.18-1.75) and maternal smoking (POR 1.16, 95%CI 1.01-1.33). Protective factors included having older siblings (two or more POR 0.69, 95%CI 0.58-0.82; one POR 0.86, 95%CI 0.71-1.05), and being born in the country of the survey (POR 0.74, 95%CI 0.63-0.87). Risk factors for rhinoconjunctivitis included regular consumption of meat, butter, margarine and nuts, regular exercise, regular television viewing, paracetamol use and passive smoking. Eczema was associated with regular meat, pasta and butter consumption, regular television viewing, paracetamol use and passive smoking. CONCLUSIONS: Regular meat and margarine consumption, paracetamol use, electric cooking and passive smoking are risk factors for symptoms of asthma, rhinoconjunctivitis and eczema in the Pacific. However, most of these associations were weak, and account for only a small proportion of cases.

Prevalence of symptoms of childhood asthma, allergic rhinoconjunctivitis and eczema in the Pacific: the International Study of Asthma and Allergies in Childhood (ISAAC).

The International Study of Asthma and Allergies in Childhood (ISAAC) has provided valuable information regarding international prevalence patterns and potential risk factors for asthma, allergic rhinoconjunctivitis and eczema. However, the only Pacific countries that participated in ISAAC Phase I were Australia and New Zealand, and these included only a small number of Pacific children. Phase III has involved not only repeating the Phase I survey to examine time trends, but also to include centres and countries which are of interest but did not participate in Phase I. The ISAAC Phase III study was therefore conducted in the Pacific (in French Polynesia, New Caledonia, Tonga, Fiji Islands, Samoa, Cook Islands, Tokelau Islands and Niue). The overall prevalence rates of current symptoms (in the last 12 months) were 9.9% for asthma, 16.4% for allergic rhinoconjunctivitis and 10.7% for atopic eczema. The prevalence of current wheezing (9.9%) was generally much lower than that has been observed in Pacific children in New Zealand (31%), but there was considerable variation between the various Pacific centres: Tokelau Islands (19.7%), Tonga (16.2%), Niue (12.7%), French Polynesia (11.3%), Cook Islands (10.6%), Fiji Islands (10.4%), New Caledonia (8.2%) and Samoa (5.8%). The reasons for these differences in prevalence across the Pacific are unclear and require further research. The finding that prevalence levels are generally considerably lower than those in Pacific children in New Zealand adds to previous evidence that children who migrate experience an altered risk of asthma as a result of exposure to a new environment during childhood.

Chest X-ray-confirmed pneumonia in children in Fiji.

OBJECTIVE: To calculate the incidence and document the clinical features of chest X-ray- (CXR-) confirmed pneumonia in children aged between 1 month and 5 years living in Greater Suva, Fiji. METHODS: A retrospective review was undertaken of children aged between 1 month and 5 years with a discharge diagnosis suggesting a lower respiratory tract infection (LRTI) admitted to the Colonial War Memorial Hospital in Suva, Fiji, in the first 10 days of each month from 1 January 2001 to 31 December 2002. Clinical data were collected and CXRs were reread and classified according to WHO standardized criteria for CXR-confirmed pneumonia. FINDINGS: Two hundred and forty-eight children with LRTI met the inclusion criteria. CXRs were obtained for 174 (70%) of these cases, of which 59 (34%) had CXR-confirmed pneumonia. The annual incidence of CXR-confirmed pneumonia was 428 cases per 100,000 children aged between 1 month and 5 years living in Greater Suva. If a similar proportion of the children for whom CXRs were unavailable were assumed to have CXR-confirmed pneumonia, the incidence was 607 per 100,000. The incidence appeared to be higher in Melanesian Fijian than Indo-Fijian children. The case-fatality rate was 2.8% in all children with LRTI, and 6.8% in those with CXR-confirmed pneumonia. CONCLUSION: This is the first study to document the incidence of CXR-confirmed pneumonia in a Pacific Island country, and demonstrates a high incidence. A significant proportion of hospital admissions of children with LRTI are likely to be preventable by the introduction of pneumococcal conjugate vaccine.