Joanna Stewart

Relationships of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity

Low serum 25 hydroxyvitamin D3 (vitamin D3) is known to perturb cellular function in many tissues, including the endocrine pancreas, which are involved in obesity and type II diabetes mellitus (TIIDM). Vitamin D3 insufficiency has been linked to obesity, whether obesity is assessed by body mass index (BMI) or waist circumference (waist). Central obesity, using waist as the surrogate, is associated with the metabolic syndrome (MetSyn), insulin resistance, TIIDM and atherosclerotic cardiovascular disease (CVD). We tested how vitamin D3 was related to measures of fat mass, MetSyn markers, haemoglobin A1c (HbA1c) and MetSyn in a cross-sectional sample of 250 overweight and obese adults of different ethnicities. There were modest inverse associations of vitamin D3 with body weight (weight) (r = -0.21, p = 0.0009), BMI (r = -0.18, p = 0.005), waist (r = -0.14, p = 0.03), [but not body fat % (r = -0.08, p = 0.24)], and HbA1c (r = -0.16, p = 0.01). Multivariable regression carried out separately for BMI and waist showed a decrease of 0.74 nmol/L (p = 0.002) in vitamin D3 per 1 kg/m2 increase in BMI and a decrease of 0.29 nmol/L (p = 0.01) per 1 cm increase in waist, with each explaining approximately 3% of the variation in vitamin D3 over and above gender, age, ethnicity and season.The similar relationships of BMI and waist with vitamin D3 may have been due to associations between BMI and waist, or coincidental, where different mechanisms relating hypovitaminosis D3 to obesity occur concurrently. Previously reviewed mechanisms include that 1) low vitamin D3, may impair insulin action, glucose metabolism and various other metabolic processes in adipose and lean tissue 2) fat soluble-vitamin D3 is sequestered in the large adipose compartment, and low in serum, 3) obese people may be sensitive about their body shape, minimising their skin exposure to view and sunlight (not tested). We showed evidence for the first theory but no evidence to support the second.In the current study, serum vitamin D3 was inversely related to weight, BMI and markers of TIIDM (large waist, raised HbA1c) but not to adipose mass nor to MetSyn per se.

Household crowding a major risk factor for epidemic meningococcal disease in Auckland children.

Background. New Zealand is in its ninth year of a serogroup B meningococcal disease epidemic with annual rates of up to 16.9 cases per 100 000. The highest incidence is in Maori and Pacific Island children in the Auckland region. We conducted a case-control study to identify potentially modifiable risk factors for this disease. Methods. A case-control study of 202 cases of confirmed and probable meningococcal disease in Auckland children younger than 8 years of age recruited from May, 1997, to March, 1999, was undertaken. Controls (313) were recruited door-to-door by a cluster sampling method based on starting points randomly distributed in the Auckland region. They were frequency matched with the expected distribution of age and ethnicity in the meningococcal disease cases. Results. With the use of a multivariate model and controlling for age, ethnicity, season and socioeconomic factors, risk of disease was strongly associated with overcrowding as measured by the number of adolescent and adult (10 years or older) household members per room [odds ratio (OR), 10.7; 95% confidence interval (CI), 3.9 to 29.5]. This would result in a doubling of risk with the addition of 2 adolescents or adults to a 6-room house. Risk of disease was also associated with analgesic use by the child, which was thought to be a marker of recent illness (OR 2.4, CI 1.5 to 4.0); number of days at substantial social gatherings (10 or more people for > 4 h; OR 1.8, CI 1.2 to 2.6); number of smokers in the household (OR 1.4, CI 1.0 to 1.8); sharing an item of food, drink or a pacifier (OR 1.6, CI 1.0 to 2.7); and preceding symptoms of a respiratory infection (cough, “cold or flu,” runny nose, sneezing) in a household member (OR 1.5, CI 1.0 to 2.5). Conclusion. Some of these identified risk factors for meningococcal disease are modifiable. Measures to reduce overcrowding could have a marked effect on reducing the incidence of this disease in Auckland children.

Delayed immunisation and risk of pertussis in infants: unmatched case-control study

Pertussis remains a severe disease in infants. As about two thirds of infants with pertussis are admitted to hospital, factors that seem to be associated with an increased risk of pertussis may in fact be associated with an increased risk of hospital admission. 1 2 The admission rate for pertussis in New Zealand is five to 10 times higher than in England and Wales and the United States.3 We determined whether immunisation reduced the risk of admission to hospital for pertussis by comparing infants admitted with pertussis and infants admitted with other acute respiratory illnesses. View this table: Odds ratios (95% confidence intervals) of catching pertussis associated with delays in giving pertussis vaccine We performed an unmatched case-control study during the 1995-7 pertussis epidemic in Auckland, New Zealand. Pertussis was defined as cough lasting at least two weeks, with coughing paroxysms, inspiratory “whoop,” or vomiting after coughing. The control group consisted of 98 infants admitted to hospital with a coughing illness who were …

Once-daily amoxicillin versus twice-daily penicillin V in group A β-haemolytic streptococcal pharyngitis

Background: Rheumatic fever is a preventable chronic disease preceded by group A β-haemolytic streptococcal (GABHS) pharyngitis. Objective: To test the non-inferiority of once-daily (QD) oral amoxicillin to the recommended twice-daily (BID) oral penicillin V in GABHS pharyngitis. Methods: This was a randomised non-inferiority trial carried out in a school-based clinic in New Zealand. Children presenting with GABHS pharyngitis were randomised to oral amoxicillin 1500 mg QD (or 750 mg if bodyweight was ⩽30 kg) or to oral penicillin V 500 mg BID (or 250 mg if bodyweight was ⩽20 kg) for 10 days. Observed medication and weekend diary cards were used to monitor adherence. Outcome: Eradication of GABHS, determined with follow-up throat cultures on days 3–6, 12–16 and 26–36. GABHS isolates were serotyped to distinguish bacteriological treatment failures (and relapses) from new acquisitions. Non-inferiority was defined as an upper 95% confidence limit (CL) for the difference in success of eradication in the amoxicillin and penicillin V treatment groups of ⩽10%. Results: 353 children with positive throat swabs for GABHS were randomised to amoxicillin (n = 177) or penicillin V (n = 176). The upper 95% CL for the differences in positive cultures between the antibiotics was 4.9% at days 3–6, 6.5% at days 12–16 and 8.5% at days 26–36. Treatment failures (including relapses) occurred at each visit in 5.8%, 12.7% and 10.7% of amoxicillin recipients and 6.2%, 11.9% and 11.3% of penicillin V recipients, respectively. No significant differences in resolution of symptoms were noted between treatment groups. One case of unsubstantiated acute rheumatic fever occurred after 7 days of amoxicillin. Conclusion: In this adequately powered study, once-daily oral amoxicillin is not inferior to twice-daily penicillin V for the treatment and eradication of GABHS in children with pharyngitis.

School-based prevention of acute rheumatic fever: a group randomized trial in New Zealand.

Background: Acute rheumatic fever (ARF) and its sequela, rheumatic heart disease is the commonest cause of childhood cardiac morbidity globally. The current approach to the prevention of a primary attack of rheumatic fever in children using oral medication for streptococcal pharyngitis is poorly supported. The efficacy of injectable penicillin, in high rheumatic fever incidence military environments is indisputable. Objective: To evaluate school-based control of rheumatic fever in an endemic area. Methods: Fifty-three schools (∼22,000 students) from a rheumatic fever high incidence setting (∼60/100,000) in Auckland, New Zealand were randomized. The control group received routine general practice care. The intervention was a school-based sore throat clinic program with free nurse-observed oral penicillin treatment of group A streptococcal pharyngitis. The outcome measure was ARF in any child attending a study school. Analysis A defined ARF cases using criteria derived from Jones Criteria 1965 (definite) and 1956 (probable) with more precise definitions. Analysis B was based on 1992 Jones criteria but also included echocardiography to determine definite cases. Results: In Analysis A, 24 (55/100,000) cases occurred in clinic schools and 29 (67/100,000) in nonclinic schools, a 21% reduction when adjusted for demography and study design (P = 0.47). Analysis B revealed a 28% reduction 26 (59/100,000) and 33 (77/100,000) cases, respectively (P = 0.27). Conclusion: This study involving 86,874 person-years showed a nonsignificant reduction in the school-based sore throat clinic programs.

New Zealand epidemic strain meningococcal B outer membrane vesicle vaccine in children aged 16-24 months

Background: New Zealand has experienced an epidemic of Neisseria meningitidis dominated by strain B:4:P1.7b,4 since 1991. Children younger than 5 years are at highest risk. Previous serogroup B outer membrane vesicle (OMV) strain specific vaccines have shown variable efficacy in this age group. Objective: To evaluate the immunogenicity, reactogenicity and safety in 16–24-month-old children of an OMV vaccine developed against the New Zealand epidemic strain. Methods: Children (332) aged 16–24 months were randomized to receive the New Zealand candidate vaccine made using strain NZ98/254 (B:4:P1.7b,4) or the Norwegian parent vaccine made using strain 44/76 (B:15:P1.7,16). Vaccines (25 μg/dose) were administered at 0, 6 and 12 weeks in this observer-blind trial. Immune response was measured by serum bactericidal assay and enzyme-linked immunosorbent assay. Sero-response was defined as a 4-fold or greater rise in serum bactericidal antibody titer compared with baseline, with titers <1:4 required to increase to ≥1:8 to be considered a sero-response. Local and systemic reactions were monitored for 7 days after vaccination. Results: Sero-response against NZ98/254 was achieved after 3 doses in 75% (95% CI: 69–80%) receiving the New Zealand candidate vaccine by both intention to treat (ITT) and per protocol (PP) analyses. In Norwegian parent vaccinees this was seen in 3% (0–12%) (ITT) and 4% (0–13%) (PP). Vaccines were well tolerated with no vaccine-related serious adverse events. Conclusion: The New Zealand candidate vaccine administered to these 16–24-month-old children in 3 doses was safe and elicited a promising immune response against the candidate vaccine strain NZ98/254 (N. meningitidis B:4:P1.7b,4) contributing to vaccine licensure for this age group.

Trends in the distribution of donor corneal tissue and indications for corneal transplantation: the New Zealand National Eye Bank Study 2000–2009

Background:  To investigate the indications for corneal transplantation and the distribution of donor corneal tissue in New Zealand.

Incidence of acute rheumatic fever in New Zealand children and youth.

Aim:  To estimate acute rheumatic fever (ARF) incidence rates for New Zealand children and youth by ethnicity, socioeconomic deprivation and region.

Immunogenicity and tolerability in infants of a New Zealand epidemic strain meningococcal B outer membrane vesicle vaccine.

Background: An outer membrane vesicle meningococcal vaccine (MeNZB), was developed for the New Zealand epidemic strain of Neisseria meningitidis B:4:P1.7-2,4. Methods: A phase II, randomized, observer blind, controlled study evaluating the safety, reactogenicity, and immunogenicity of MeNZB administered with routine New Zealand immunizations at 6 weeks, 3 months, and 5 months of age (n = 375). Group 1 (n = 250) received 25 μg MeNZB and routine immunizations with a fourth MeNZB dose given at 10 months (n = 51). Group 2 (n = 125) received routine immunizations only. Sero-response was a ≥4-fold rise in vaccine strain serum bactericidal antibody titer compared with baseline or a titer of at least 1:8 for baselines <1:4. Reactogenicity was monitored for 7 days after vaccination. Results: Sero-response in Group 1 was achieved in 53% (95% Confidence interval [CI]: 46–59, n = 239) and 69% (95% CI: 54–80, n = 45) with geometric mean antibody titers of 9 (95% CI: 7–10) and 22 (95% CI: 12–39) after the third and fourth doses, respectively. No negative interference by MeNZB on routine immunizations was detected. There were no serious adverse events judged to be vaccine related. Conclusions: In this group of New Zealand infants, 4 MeNZB doses were required to demonstrate titers comparable with those achieved after 3 doses in older children. MeNZB was safe when used concomitantly with routine New Zealand immunizations to 5 months of age.

Fast Tracking the Vaccine Licensure Process to Control an Epidemic of Serogroup B Meningococcal Disease in New Zealand

Epidemics of serogroup B meningococcal disease are rare. Strain-specific outer membrane vesicle vaccines, which are not marketed, are the only current tool for control. A correlate of protection is ill defined, but published data suggest that measured serum bactericidal antibody levels parallel efficacy. Even infants can mount a strain-specific antibody response to a strain-specific vaccine. New Zealands epidemic (1991-2007; peak rate [in 2001], 17.4 cases per 100,000 persons) was dominated by a single strain. After a 5-year search (1996-2001) for a manufacturer for a strain-specific outer membrane vesicle vaccine, a fast-tracked research program (2002-2004) determined the safety and immunogenicity of vaccine in infants (2 age groups: 6-10 weeks and 6-8 months), children (age, 16-24 months), and school-aged children (age, 8-12 years) after an adult trial. The vaccine was reactogenic, compared with control vaccines (meningococcal C conjugate and routine infant vaccines), but retention was high. Three vaccine doses produced antibody levels (measured by serum bactericidal assay) that were considered to be adequate for public health intervention. However, in young infants, a fourth dose was required to achieve levels equivalent to those achieved by other age groups. Provisional licensure by New Zealands MedSafe was based on serological criteria strengthened by bridged safety data from studies of the parent outer membrane vesicle vaccine, independent assessment of manufacturing quality, and a clear plan for safety monitoring and effectiveness evaluation after licensure.