The New Zealand Blood Donors' Health Study: baseline findings of a large prospective cohort study of injury.

INTRODUCTION: Cohort studies have contributed important scientific knowledge regarding the determinants of chronic diseases. Despite the need for etiologic investigations, this design has been infrequently used in injury prevention research. OBJECTIVES: To describe the baseline findings of the New Zealand Blood Donors' Health Study, a large prospective study designed to investigate relationships between lifestyle, psychosocial factors, and serious injury due to road crashes, falls, self harm, assault, work, sport, and recreation. METHODS: Participants were recruited from fixed and mobile collection sites of a voluntary non-profit blood donor program. Baseline exposure data (for example risk taking behaviors, alcohol and marijuana use, sleep habits, and depression) were collected using a self administered questionnaire. Outcome data regarding serious injury will be collected prospectively through computerized record linkage of participants' unique identifiers to national morbidity and mortality databases. RESULTS: In total, 22 389 participants enrolled in the study (81% response rate). The diverse study population included 36% aged 16-24 years, 20% rural residents, and large variability in exposures of interest. For example, in the 12 months before recruitment, 21% had driven a motor vehicle when they considered themselves over the legal limit for alcohol, and 11% had been convicted of traffic violations (excluding parking infringements). Twelve per cent had seriously considered attempting suicide sometime in their life. CONCLUSIONS: This is the first, large scale cohort study investigating determinants of serious injury in New Zealand and among the largest worldwide. Preliminary findings from prospective analyses that can inform injury prevention policy are expected within five years.

A prospective cohort study of blood donors: methodological issues in the investigation of injuries and chronic diseases.

Blood donors have made important contributions to research, most notably in cross-sectional seroprevalence studies. The proposed New Zealand Blood Donors Health Study is a prospective cohort study of 30,000 New Zealand donors designed to investigate the determinants of common injuries, cardiovascular disease and cancer. While robust from an analytic perspective, the execution of prospective cohort studies in many settings is impeded by methodological, economic and organisational barriers. We examined the operational considerations of implementing a large-scale cohort study at a transfusion centre and evaluated measures taken to optimise data collection procedures. A pilot study of 1,000 participants revealed donor motivation to participate in this research was high (91% response rate). Comprehensive exposure data on lifestyle, behavioural and psychosocial factors were obtained from 95% of participants. Substantial heterogeneity in levels of potential risk factors was noted among respondents. Detailed dietary habit information and a study blood sample were obtained from 67% and 100% of participants, respectively. Study recruitment and baseline data collection was feasible during routine donor visits with minimal interruption to donor centre staff and procedures. We conclude the study design and characteristics of the regional donor program enhance the efficiency and significance of the proposed research.

Clinical usage of intravenous immunoglobulins in Auckland.

AIMS: To review the indications for prescription of intravenous immunoglobulin (IVIg), in Auckland and the associated adverse effects. METHODS: All patients who received IVIg infusions in four major hospitals in Auckland in 1996 were identified from blood bank records. Clinical details were recorded from case notes. RESULTS: One hundred and thirty-five cases were identified and 131 records were available for review. Hypogammaglobulinaemia (n = 38) and thrombocytopenia (n = 38) were the two most common indications for 44% of Primary hypogammaglobulinaemia accounted for IVIg. the IVIg prescribed. IVIg was only used in one patient with hypogammaglobulinaemia secondary to chronic lymphocytic leukaemia and in one case of graft-versus-host disease. Adverse reactions were noted in 13 cases (10%). Headache (n = 4) and fever (n = 4) were the most commonly recorded side-effects. One patient developed acute renal failure after IVIg infusion. Written consent was documented in 7 patients (5%). CONCLUSIONS: The indications for IVIg prescription were generally consistent with the recommendations of the Australasian Society of Blood Transfusion. Use of IVIg in haematological conditions other than immune thrombocytopaenic purpura was infrequent. Most of the IVIg infusions were administered uneventfully but some minor side effects were recorded and one significant clinical event may have been causally related to IVIg infusion.

Clinical and molecular aspects of Gaucher disease in New Zealand.

AIM: To report on the clinical and molecular aspects of Gaucher disease in New Zealand. METHODS: Patients known to have Gaucher disease were contacted and clinical information was recorded by questionnaire. Blood samples from affected individuals and their families provided DNA material for mutation analysis of disease causing alleles. Patients were assayed for beta-glucocerebrosidase, the enzyme deficiency which causes Gaucher disease. RESULTS: Twelve of 14 patients and 10 carriers were confirmed by DNA analysis. One asymptomatic individual was diagnosed. Four known mutations (N370S, 1444p, R463c and RecNcIl) and one unknown mutation were found from the 34 disease producing alleles that were identified. Of these, the L444P and N370S alleles were the most common. Most patients exhibited a clinical disorder typical of type 1 Gaucher disease. Two recent patients with severe neuropathic Gaucher disease had died in childhood. All patients showed a deficiency in beta-glucocerebrosidase. CONCLUSION: Gaucher disease in New Zealand is represented in a small number of non Jewish individuals with varying severity. Identifiable mutations and clinical symptoms aid in expanding the Australasian picture of this well studied disease. Enzyme replacement therapy for these patients has recently commenced in New Zealand.

HLA-B27 polymorphism and worldwide susceptibility to ankylosing spondylitis.

HLA-B27 is strongly associated to ankylosing spondylitis (AS) and represents a family of eleven B27 alleles (B*2701-11). Our aim was to analyze the distribution of B27 subtypes by PCR/SSOP and genomic sequencing in a large group of populations (n = 17). 711 B27-positive samples from Caucasoid, Asian, African, Amerindian and Polynesian populations were selected to ascertain transracial gene mapping of the B27 subtypes. 476 of these were AS patients, chosen to investigate the contribution of B27 alleles to AS susceptibility. Some significant new findings have arisen from this study: 1) B*2705 was the predominant subtype in circumpolar and subarctic areas. B*2702 was found to be practically restricted to Caucasian populations, showing a higher frequency in Middle-East (Jews) and North Africa (Arabs/Berbers) groups. 2) B*2703 appears associated with AS in Western Africans. This is of remarkable interest since it was suggested that B*2703 would be negatively disease-associated. 3) Although B*2706 appears negatively associated with AS in Thais, we identified two patients from northern China carrying it. This may be a reflection of a disease heterogeneity and could indicate that more than one pathogenic agent can be involved in AS. B*2709 has been recently described as negatively associated with AS in Sardinians. The molecular changes His114Asp (B*2706) and Asp116His (B*2709) could modify the genetic susceptibility to AS.

Transfusion transmitted Yersinia enterocolitica infection in New Zealand.

AIMS: To update and summarise cases of transfusion-transmitted Yersinia enterocolitica infection in New Zealand and to evaluate critically suggested methods to reduce this rare but frequently fatal complication of blood transfusion. METHODS: Case reports of four recent transfusion-transmitted Y. enterocolitica infections in New Zealand are given and previous reports reviewed. Literature review and evaluation of proposed methods to decrease the incidence of transfusing yersinia contaminated blood. RESULTS: There have been eight cases of transfusion-transmitted Y. enterocolitica infection in New Zealand in the past five years. Four of the five deaths have been directly caused by the transfusion. This gives a transfusion incidence rate of one:65,000 and a fatality rate of one:104,000 units transfused. This fatality rate is more than 80 times higher than that reported in the United States. CONCLUSIONS: Why the incidence of transfusion-transmitted yersinia is so high is not clear, since we do not store blood as long as many other countries, particularly the United States. In Auckland, however, the cases came at a time when the number of yersinia isolates from the community is reported to be rising. Many suggestions for the prevention of this problem have been put forward reflecting the fact that there is as yet no perfect solution. Those which are easy to implement and cheap to perform are largely already in place and investigation is continuing into the other alternatives.

Donor work-up and transport of bone marrow--recommendations and requirements for a standardized practice throughout the world from the Donor Registries and Quality Assurance Working Groups of the World Marrow Donor Association (WMDA).

In October 1995 the World Marrow Donor Association (WMDA) was restructured in order to facilitate its primary function of establishing guidelines in relation to international bone marrow and blood stem cell transplants -- transplants in which the donor is in one country and the patient is in another country. Five new working groups were established -- Donor Registries, Ethics, Quality Assurance, Finances, and Stem Cells. This paper, prepared by members of the Donor Registries Working Group, in consultation with the Quality Assurance Working Group, provides recommendations for the 'donor work-up'. This term covers events that start when the definitive donor has been identified, includes the harvesting (collection) and transportation of the stem cell product and ends when the product reaches the transplant centre. The paper includes examples of the documentation intended to ensure compliance with the recommendations at all key points in the sequence.

Alpha-2-HS-glycoprotein polymorphism in New Zealand Europeans and New Zealand Maori.

The polymorphism of alpha-2-HS-glycoprotein (AHSG, alpha 2HS) was analysed in a sample of New Zealanders consisting of 194 New Zealand Europeans and 236 New Zealand Maori. Thin layer polyacrylamide gel isoelectric focusing followed by immunofixation revealed four different AHSG phenotypes in New Zealand Europeans and three different AHSG phenotypes in New Zealand Maori. The AHSG*2 frequency of 0.695 for the New Zealand Maori population was found to be one of the highest reported for any population. AHSG*2 appears to be a useful genetic marker for Maori in anthropological studies.

Entire nucleotide sequence and characterization of a hepatitis C virus of genotype V/3a.

The entire nucleotide sequence of a hepatitis C virus (HCV) genome (NZL1) of genotype V/3a was determined from overlapping cDNA clones obtained from a human carrier in New Zealand. It comprised 9425 nucleotides (nt) including a 5'-untranslated region of 339 nt, a single large open reading frame encoding a polyprotein of 3021 amino acids, a 3'-untranslated region of 23 nt, and 3'-terminal poly(U) stretches of variable lengths. The NZL1 genome was compared with 15 HCV isolates of other genotypes for which the full-length sequence has been determined. It differed from them by 31.1 to 34.3% in nucleotide sequence identity and by 24.5 to 29.1% in amino acid sequence identity, confirming the distinction of genotype V/3a from the other isolates.

The genetic affinity of Polynesians: evidence from Y chromosome polymorphisms.

Y-linked polymorphisms were studied in a sample of 60 Polynesians, and results were compared with findings from studies on other major population groups. Three previously unreported 49a/TaqI haplotypes were observed, two of which possess a new polymorphic fragment named I2. Frequency data for the 49a/TaqI, XY275, pDP31 and Y Alu polymorphisms indicate that Polynesians have greater affinity to Caucasoids than to African populations. Similar population frequency trends were not observed for the p21A1/TaqI polymorphism, supporting the hypothesis that this polymorphism has arisen more than once.

Identification and genotyping of hepatitis C virus in injectable and oral drug users in New Zealand.

BACKGROUND: Hepatitis C virus infections are known to be common in injectable drug users (IDU) both in New Zealand and overseas. Little is known of the hepatitis C genotype frequency in this population. AIMS: To confirm the high incidence of hepatitis C virus infections in IDU and compare this with the frequency in oral drug users (ODU) as well as identify the pattern of hepatitis C genotypes present. METHODS: Use was made of an experimental nucleocapsid assay as well as a conventional anti-HCV assay. HCV-RNA was identified using a polymerase chain reaction (PCR) technique and a variation of this method was used for HCV genotyping. RESULTS: Seventy-four per cent of IDU were reactive for anti-HCV in both types of assay. PCR testing detected several more reactive samples. Dominant genotypes were Types I and V, but Type IV was not detected. Mixed infections were noted in some patients. There was a low frequency of anti-HCV in ODU. CONCLUSIONS: Hepatitis C virus infections are a problem in IDU in New Zealand, and additional public health measures may be required. The distribution of genotypes of HCV-RNA are similar to those seen in other Western countries.

A possible relationship between colorectal carcinoma and ABO/Lewis blood groups.

The incidence of colorectal carcinoma was compared with the incidence of ABO and Lewis blood groups. The raw data showed the known overrepresentation of the Le(a-b) phenotype, but also suggested an association of colorectal carcinoma with the Le(a-b+) phenotype in group O individuals. When the data were adjusted by taking into account the known loss of Lewis antigens by Lewis-positive patients, this association could be shown to be statistically significant. These results may indicate involvement of the secretory H antigen in colorectal carcinoma.

T cell receptor polymorphisms in Caucasians and Polynesians.

The purpose of this study was to find genetic polymorphisms that might be useful in studies of Polynesian-Caucasian racial admixture and Polynesian disease susceptibility. The allele frequencies of six T cell receptor locus RFLP were measured in 73 Caucasians and two Polynesian ethnic groups comprising 86 Maoris and 95 Samoans. The RFLP studied were (locus/enzyme/probe): C alpha/Taq1/Y14, V alpha/Taq1/Y14, C beta/BglII/Y35, C gamma/Pvu II/HGP02, V beta 7/BamHI/V beta 7.4 and V beta 8/Bam HI/V beta 8.1. Racial differences in allele frequency were present with all six RFLP (P < 0.001). The allele frequencies of the V alpha/Taq1/Y14 and the V beta 7/BamHI/7.4 RFLP were similar in the two Polynesian groups, both of which differed from the Caucasians. The 1.4 kb allele of the V alpha/Taq1/Y14 RFLP and the 8.0 kb allele of the V beta 7/BamHI/7.4 RFLP were present in low frequency in both Polynesian groups compared to the Caucasian group, consistent with a gene flow effect. These alleles may be useful in studies of Caucasian-Polynesian racial admixture.

The persistence of anti-hepatitis B surface antibodies to three years of age: is a hepatitis B vaccine booster required?

AIMS: To evaluate the persistence of hepatitis B surface antibodies (anti-HBs) after immunisation in early infancy. METHODS: The infants were born to low risk European mothers negative for hepatitis B surface antigen (HBsAg). All the children had received 3 doses of 20 micrograms of recombinant DNA hepatitis B vaccine. RESULTS: One month after the third dose all 92 infants were seropositive. The GMT was 1190 mIU/mL and all but one infant had seroprotective titres above 10 mIU/mL. Three years after the vaccination 91% (59 of 65) children who returned for testing still had measurable anti-HBs titres. The GMT was 32 mIU/mL but 26% (17 of 65) had titres less than 10 mIU/ml. Only one child had serologic evidence of contact with the hepatitis B virus but did not develop the disease. CONCLUSION: This vaccine is safe and effective for at least 3 years. The long term duration of protection from vaccination in early infancy requires further studies.

Unlinked anonymous monitoring of HIV prevalence at sexually transmitted disease clinics.

AIM: To determine the prevalence of HIV infection among patients attending the four sexually transmitted disease (STD) clinics in two metropolitan areas of New Zealand. METHODS: The population studied comprised everyone who attended between August 1991 and August 1992 because of concern about a possible new episode of an STD and who had a blood specimen taken for hepatitis B (or syphilis) serology. The study involved unlinked anonymous testing of left-over blood specimens, following ethical guidelines that have been proposed internationally. RESULTS: Among 8478 specimens tested, 23 (2.7 per 1000) were found to be HIV positive. The seroprevalence rates per 1000 among women, heterosexual men, and homosexual or bisexual men were 1.1, 1.3, and 44, respectively. All but five of the infected people were either known to be HIV positive or had an identifiable test during their clinic attendance. CONCLUSIONS: The seroprevalence rates are similar to those reported from STD clinics in England, and suggest that heterosexual transmission of HIV infection has not yet been extensive in New Zealand.