ABSTRACT
BACKGROUND AND OBJECTIVES: The rate of confirmed hepatitis C virus (HCV) cases, in first-time donors, is much lower in 2015 than 20 years ago. We investigate reasons for the decline. MATERIALS AND METHODS: HCV rates were analysed by gender and birth cohort for 1996 to 2015 and ethnic group for 2006 to 2015. Variables for confirmed positive cases were compared for two ten-year periods (1996 to 2005 and 2006 to 2015) including genotyping data for 2006 to 2015. RESULTS: There were 2007 confirmed HCV cases identified between 1996 and 2015. The rate per 100 000 donations fell from 78·6 in 1996 to 26·9 by 2015. By birth cohort, HCV rates were highest in donors born in the 1950s and 1960s who contributed a decreasing proportion of first-time donors. Between 2006 and 2015, there was no significant decline in HCV rate. The HCV-positive donor profile has changed in the last 10 years with increased proportions of younger donors, donors born abroad and decreased reported injecting drug use. Genotype 1a remains predominate, but genotype 1b has increased associated with this change in birth cohort and ethnicity. CONCLUSION: The decline in number and rate of confirmed HCV-positive first-time donors is mainly due to a decrease in first-time donors born before 1970, with the highest rate of HCV. However, the decline has slowed and the profile of HCV-positive first-time donors is changing. A better understanding of behaviour and sources of HCV in younger and ethnic minority donors are needed.
Subject(s)
Blood Donors/statistics & numerical data , Hepacivirus/isolation & purification , Hepatitis C/epidemiology , England , Female , Genotype , Hepacivirus/genetics , Hepatitis C/blood , Humans , Male , Serologic Tests , WalesSubject(s)
Blood Donors , Donor Selection , Malaria, Vivax , Plasmodium vivax , Adult , Humans , Malaria, Vivax/blood , Malaria, Vivax/diagnosis , MaleABSTRACT
The genomic sequences of 20 Leishmania infantum isolates collected in northeastern Brazil were compared with each other and with the available genomic sequences of 29 L. infantum/donovani isolates from Nepal and Turkey. The Brazilian isolates were obtained in the early 1990s or since 2009 from patients with visceral or non-ulcerating cutaneous leishmaniasis, asymptomatic humans, or dogs with visceral leishmaniasis. Two isolates were from the blood and bone marrow of the same visceral leishmaniasis patient. All 20 genomic sequences display 99.95% identity with each other and slightly less identity with a reference L. infantum genome from a Spanish isolate. Despite the high identity, analysis of individual differences among the 32 million base pair genomes showed sufficient variation to allow the isolates to be clustered based on the primary sequence. A major source of variation detected was in chromosome somy, with only four of the 36 chromosomes being predominantly disomic in all 49 isolates examined. In contrast, chromosome 31 was predominantly tetrasomic/pentasomic, consistent with its regions of synteny on two different disomic chromosomes of Trypanosoma brucei. In the Brazilian isolates, evidence for recombination was detected in 27 of the 36 chromosomes. Clustering analyses suggested two populations, in which two of the five older isolates from the 1990s clustered with a majority of recent isolates. Overall the analyses do not suggest individual sequence variants account for differences in clinical outcome or adaptation to different hosts. For the first known time, DNA of isolates from asymptomatic subjects were sequenced. Of interest, these displayed lower diversity than isolates from symptomatic subjects, an observation that deserves further investigation with additional isolates from asymptomatic subjects.
Subject(s)
Dog Diseases/parasitology , Leishmania infantum/genetics , Leishmaniasis, Visceral/veterinary , Animals , DNA, Protozoan/genetics , Dog Diseases/epidemiology , Dogs , Genetic Variation , Genome, Protozoan , Humans , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/parasitology , Polymorphism, Single NucleotideABSTRACT
An outbreak of locally acquired Plasmodium vivax malaria in Greece started in 2009 and peaked in 2011. Targeting of blood safety measures to affected areas with ongoing transmission of malaria raised questions of how to define spatial boundaries of such an area and when to trigger any specific blood safety measures, including whether and which blood donation screening strategy to apply. To provide scientific advice the European Centre for Disease Prevention and Control (ECDC) organised expert meetings in 2013. The outcomes of these consultations are expert opinions covering spatial targeting of blood safety measures to affected areas with ongoing local transmission of malaria and blood donation screening strategy for evidence of malaria infection in these areas. Opinions could help EU national blood safety authorities in developing a preventive strategy during malaria outbreaks.
Subject(s)
Blood Donors , Blood Safety , Donor Selection/methods , Malaria, Vivax/prevention & control , Malaria, Vivax/transmission , Plasmodium vivax , Congresses as Topic , Donor Selection/standards , Female , Greece , Humans , Malaria, Vivax/epidemiology , MaleABSTRACT
BACKGROUND AND OBJECTIVES: The English transfusion service has screened donations from malaria-risk donors for malarial antibodies for over 10 years. The donor population includes migrants from many malaria-endemic countries and, from our experiences with post-transfusion malaria, some of these may remain parasitaemic and need clinical review. MATERIALS AND METHODS: Malarial antibody screen-reactive donations with serological evidence of malaria identified by the reference laboratory were further investigated for the presence of malarial DNA. RESULTS: Malarial DNA was found in 14 of 1955 samples investigated; three P. falciparum, five P. vivax, three P. ovale, two P. malariae and one dual parasitaemia P. falciparum/P. malariae. All of these were donors whose malaria risk was residency rather than travel. CONCLUSION: Malarial parasitaemia in healthy donors occurs, and donor malaria-risk strategies must take into account the possibility of such donors presenting. Countries not utilizing malarial antibody screening should consider carefully the collection of donations from donors previously resident in endemic countries; temporary deferral is insufficient.
Subject(s)
Blood Donors , DNA, Protozoan/blood , Malaria/blood , Parasitemia/blood , Plasmodium/immunology , Adult , Antibodies, Protozoan/blood , Antigens, Protozoan/blood , Blood Safety , Female , Humans , Malaria/diagnosis , Malaria/immunology , Male , Parasitemia/diagnosis , Parasitemia/immunology , Plasmodium/genetics , Young AdultABSTRACT
A comprehensive and effective screening programme is essential to support the banking of tissues from deceased donors. However, the overall quality of the samples obtained from deceased donors, quantity and condition, is often not ideal, and this may lead to problems in achieving accurate and reliable results. Additionally a significant percentage of referrals are still rejected upon receipt as unsuitable for screening. We are actively involved in improving the overall quality of deceased donor screening outcomes, and have specifically evaluated and validated both serological and molecular assays for this purpose, as well as developing a specific screening strategy to minimise the specificity issues associated with serological screening. Here we review the nature and effectiveness of the deceased donor screening programme implemented by National Health Service Blood and Transplant (NHSBT), the organisation with overall responsibility for the supply of tissue products within England. Deceased donor screening data, serological and molecular, from August 2007 until May 2012 have been collated and analysed. Of 10,225 samples referred for serology screening, 5.5 % were reported as reactive; of 2,862 samples referred for molecular screening, 0.1 % were reported as reactive/inhibitory. Overall 20 % of the serological and 100 % of the molecular screen reactivity was confirmed as reflecting true infection. The use of a sequential serology screening algorithm has resulted in a marked reduction of tissues lost unnecessarily due to non-specific screen reactivity. The approach taken by NHSBT has resulted in the development of an effective and specific approach to the screening of deceased tissue donors.
Subject(s)
Donor Selection/methods , Pathology, Molecular/methods , Serology/methods , Tissue Donors , Humans , Reproducibility of ResultsABSTRACT
Whilst some of the assays used for serological screening of post-mortem blood samples from deceased tissue donors in some countries have been specifically validated by the manufacturer for this purpose, a significant number of those currently in use globally have not. Although specificity has previously been considered a problem in the screening of such samples, we believe that ensuring sensitivity is more important. The aim of this study was to validate a broader range of assays for the screening of post-mortem blood samples from deceased tissue donors. Six microplate immunoassays currently in use within National Health Service Blood and Transplant (NHSBT) for the screening of blood, tissue and stem cell donations were included. Representative samples from confirmed positive donors were titrated in screen negative post-mortem samples in parallel with normal pooled negative serum to determine if there was any inhibition with the post-mortem samples. There were no significant differences seen (P < 0.005) between the dilution curves obtained for the positive samples diluted in post-mortem samples and normal pooled sera. Although small numbers of samples were studied, it can be surmised that the post-mortem blood samples from deceased tissue donors, collected according to United Kingdom guidelines, are a suitable substrate for the assays evaluated. No diminution of reactivity was seen when dilution with sera from deceased donors was compared to dilution using pooled serum from live donors. In the absence of genuine low titre positive post-mortem samples, the use of samples spiked with various levels of target material provides a means of qualifying serological screening assays used by NHSBT for the screening of post-mortem blood samples from deceased tissue donors.
Subject(s)
Communicable Diseases/blood , Communicable Diseases/diagnosis , Immunoassay/methods , Tissue Donors , Adult , Aged , Cadaver , Female , Humans , Male , Middle Aged , Young AdultSubject(s)
Antibodies, Protozoan/blood , Blood Donors , Malaria/prevention & control , Plasmodium/immunology , Transfusion Reaction , Antigens, Protozoan/immunology , Brazil/epidemiology , Carrier State/blood , Carrier State/diagnosis , DNA, Protozoan/blood , Endemic Diseases , Enzyme-Linked Immunosorbent Assay , Europe/epidemiology , Fluorescent Antibody Technique, Indirect , Humans , Israel/epidemiology , Malaria/blood , Malaria/diagnosis , Malaria/epidemiology , Malaria/transmission , New Zealand/epidemiology , Nucleic Acid Amplification Techniques , United States/epidemiologyABSTRACT
BACKGROUND AND OBJECTIVES: Monitoring of the ongoing performance of infectious disease screening assays is a critical part of any donation screening programme. Although assay sensitivity is formally evaluated prior to implementation, it is essential that this level of performance is maintained from lot-to-lot. In 2002, National Health Service Blood and Transplant developed and implemented a formal system for the lot release testing of serology infectious disease screening assays. MATERIALS AND METHODS: Lot release panels were prepared for each of the serological screening markers. They each comprise 10-15 members and include both genuine low-titre and diluted high-titre materials. For each panel member, a minimum reactivity is expected, based upon the formal sensitivity evaluation of each assay. All new lots of the screening assays used are assessed prior to supply of the lot to the organization. RESULTS: Since 2002, a total of 887 different lots of the serology screening assays used have been supplied. Of these, 876 (98.8%) passed lot release and were authorized for supply to the organization. Eleven lots (1.2%) were failed because the lots did not meet the release criteria or were unsuitable for some other reason. CONCLUSION: The lot release system has proved to be effective in objectively assessing assay performance to ensure that there is no significant lot-to-lot variation such that the performance of the assay may fall below that originally determined at evaluation. The few assays that have failed lot release did have proven performance issues that were subsequently accepted by the manufacturers. CONTENTS SUMMARY: Description of the Lot Release Testing system for serology infectious disease screening assays in use within NHSBT with a critical analysis and review of the data generated in the 7 years that the system has been in use.
Subject(s)
Blood Donors , Blood Transfusion/standards , Infections/blood , Blood-Borne Pathogens , Humans , Infection Control/methods , Mass Screening/methodsABSTRACT
BACKGROUND AND OBJECTIVES: The overall effectiveness of the NHSBT screening programme for infectious agents in deceased tissue donors is examined and evaluated in terms of current outcomes and how to improve upon these outcomes. MATERIALS AND METHODS: The screening results and any subsequent confirmatory results from a total of 1659 samples from NHSBT deceased donors referred to NTMRL for screening for infectious agents were included in the analysis. RESULTS: Overall 1566/1659 (94.4%) of the samples were screen negative. A total of 93 were repeat reactive on screening for one or more of the mandatory markers screened for, of which only 12 (13%) were subsequently confirmed to be positive on confirmatory testing. The majority of the repeat reactive samples were demonstrating non-specific reactivity with the screening assays in use. CONCLUSION: Overall, the NHSBT screening programme for infectious agents in deceased tissue donors is very effective with a relatively low overall loss of donors because of non-specific reactivity. However, unnecessary loss of tissue products is not acceptable, and although this programme compares favourably with the outcomes of other such programmes, the confirmatory results obtained demonstrate both the need and the potential for improving the outcomes. This is particularly important as one donor may donate more than one product, and can be achieved very easily with a change to the screening algorithm followed, using the confirmatory data obtained to support and validate this change. CONTENTS SUMMARY: Critical analysis of the NHSBT screening programme for infectious agents in deceased tissue donors and a strategy involving the design and use of a different screening algorithm to improve these outcomes.
Subject(s)
Blood-Borne Pathogens , Infection Control/organization & administration , Mass Screening , National Health Programs/organization & administration , Tissue Donors , England , Forecasting , Humans , Program EvaluationABSTRACT
We report two instances of human immunodeficiency virus (HIV) serological screening reactivity in blood donations which were subsequently determined to be due to donor participation in HIV vaccine trials. Both donations were screen reactive with atypical patterns on confirmation; no definitive conclusion could be given for either donor. Subsequent questioning identified that both donors had been involved in HIV vaccine trials. In both cases the screening and confirmation identified the presence of HIV antibodies, although vaccine induced. While clinical trials of vaccines are important, the implications of some need careful consideration if they are not to adversely impact other areas of healthcare.
Subject(s)
AIDS Vaccines/immunology , Blood Donors , Diagnostic Errors , HIV Antibodies/blood , HIV Infections/diagnosis , Adult , Female , HIV Infections/transmission , Humans , Mass Screening , Transfusion ReactionABSTRACT
The Transfusion Microbiology Test Systems Monitoring Group (TMTSMG) was established as a National Blood Service (NBS) working group to monitor the performance of the microbiology screening assays used within the NBS Testing Laboratories. The group's primary objective was to ensure that technical performance (especially sensitivity, specificity and wastage) remains consistent with that established during validation. This includes the identification and investigation of significant variation in performance and any untoward incidents. The group is also responsible for optimizing transfusion microbiology working practice across the NBS through nationally agreed standards and procedures. Over the past 9 years, a total of 44 assays from 15 suppliers have been monitored. Five assays have been withdrawn from use as a result of identified poor performance; two hepatitis B virus surface antigen assays owing to poor sensitivity, two syphilis agglutination assays with nonspecific (false) reactive rates sustained above contract limits and one human cytomegalovirus antibody assay that persistently failed the manufacturer's quality control criteria. This approach has enabled the differentiation of genuine kit performance issues from 'natural variation' in kit performance, and local instrumentation or training issues. The NBS has been able to address the issues with suppliers much earlier and resolve minor issues before they became major problems. In addition, a lot release system has been developed and implemented, comprising a formal, centralized initial scientific assessment of each new manufacturer's lot, followed by 'delivery acceptance' testing at each site. This system helps to ensure that the evaluated minimum sensitivity and specificity of the assays is maintained from 'lot to lot'.
Subject(s)
Blood Banks/standards , Blood Transfusion/standards , Quality Assurance, Health Care/standards , Reagent Kits, Diagnostic/microbiology , Reagent Kits, Diagnostic/standards , Blood-Borne Pathogens , England , Humans , Quality Control , Sensitivity and SpecificityABSTRACT
Analysis of complete mitochondrial genome sequences is becoming increasingly common in genetic studies. The availability of full genome datasets enables an analysis of the information content distributed throughout the mitochondrial genome in order to optimize the research design of future evolutionary studies. The goal of our study was to identify informative regions of the human mitochondrial genome using two criteria: (1) accurate reconstruction of a phylogeny and (2) consistent estimates of time to most recent common ancestor (TMRCA). We created two series of datasets by deleting individual genes of varied length and by deleting 10 equal-size fragments throughout the coding region. Phylogenies were statistically compared to the full-coding-region tree, while coalescent methods were used to estimate the TMRCA and associated credible intervals. Individual fragments important for maintaining a phylogeny similar to the full-coding-region tree encompassed bp 577-2122 and 11,399-16,023, including all or part of 12S rRNA, 16S rRNA, ND4, ND5, ND6, and cytb. The control region only tree was the most poorly resolved with the majority of the tree manifest as an unresolved polytomy. Coalescent estimates of TMRCA were less sensitive to removal of any particular fragment(s) than reconstruction of a consistent phylogeny. Overall, we discovered that half the genome, i.e., bp 3669-11,398, could be removed with no significant change in the phylogeny (p(AU)=0.077) while still maintaining overlap of TMRCA 95% credible intervals. Thus, sequencing a contiguous fragment from bp 11,399 through the control region to bp 3668 would create a dataset that optimizes the information necessary for phylogenetic and coalescent analyses and also takes advantage of the wealth of data already available on the control region.
Subject(s)
Genome, Mitochondrial , Phylogeny , Chromosome Mapping , DNA, Mitochondrial/genetics , Databases, Genetic , Evolution, Molecular , Genetic Techniques , Genome, Human , HumansABSTRACT
We investigated the evolution of 6 genes from the Treponema pallidum repeat (tpr) gene family, which encode potential virulence factors and are assumed to have evolved through gene duplication and gene conversion events. The 6 loci (tprC, D, G, J, I, and K) were sequenced and analyzed in several members of the genus Treponema, including the 3 subspecies of human T. pallidum (T. pallidum subsp. pallidum, pertenue, and endemicum), Treponema paraluiscuniculi (rabbit syphilis), and the unclassified Fribourg-Blanc (simian) isolate. Phylogenetic methods, recombination analysis, and measures of nucleotide diversity were used to investigate the evolutionary history of the tpr genes. Numerous instances of gene conversion were detected by all 3 methods including both homogenizing gene conversion that involved the entire length of the sequence as well as site-specific conversions that affected smaller regions. We determined the relative age and directionality of the gene conversion events whenever possible. Our data are also relevant to a discussion of the evolution of the treponemes themselves. Higher levels of variation exist between the human subspecies than within them, supporting the classification of the human treponemes into 3 subspecies. In contrast to published theories, the divergence and diversity of T. pallidum subsp. pertenue relative to the other subspecies does not support a much older origin of yaws at the emergence of modern human, nor is the level of divergence seen in T. pallidum subsp. pallidum consistent with a very recent (< 500 years) origin of this subspecies. In general, our results demonstrate that intragenomic recombination has played a significant role in the evolution of the studied tpr genes and emphasize that efforts to infer evolutionary history of the treponemes can be complicated if past recombination events are not recognized.
Subject(s)
Evolution, Molecular , Genes, Bacterial , Phylogeny , Recombination, Genetic , Treponema pallidum/genetics , Animals , Gene Duplication , Humans , Molecular Sequence Data , Polymerase Chain Reaction , Rabbits , Sequence Alignment , Treponema pallidum/isolation & purificationABSTRACT
The transmission of malaria by blood transfusion was one of the first recorded incidents of transfusion-transmitted infection. Although a number of different infections have been reported to be transmitted by transfusion since then, on a global scale malaria remains one of the most common transfusion-transmitted infections. Transfusion-transmitted malaria can have serious consequences, as infection with Plasmodium falciparum may prove rapidly fatal. Ensuring that, in non-endemic countries, the blood supply is free from malaria is problematical, especially as travel to malarious areas is increasing and there is some spread of the disease into new areas, as well as a resurgence of malaria in areas where previously it had been eradicated. In non-endemic countries, donor deferral can be effective, but clear guidelines are needed. In endemic countries the problem is far greater as the majority of donors may be potentially infected with malaria parasites. In both situations, the simple deferral of donors may be wasteful and can eventually erode the donor base. Thus, other strategies are needed to ensure safety with sufficiency. However, the screening of donations for evidence of malaria is not without its problems. Although the examination of blood films is still the basis for diagnosing acute malaria, in most situations it is not sufficiently sensitive for blood bank screening. In non-endemic countries, donor deferral in combination with screening for specific antimalarial immunoglobulin provides an effective means of minimizing the risk of transmission. In endemic countries, more specific donor questioning, consideration of seasonal variation and geographical distribution may help to identify the population of donors who are most likely to be infected. In addition, the administration of antimalarials to transfusion recipients may help to prevent transmission. Nonetheless, no matter what strategy is adopted, it is likely that cases of transfusion-transmitted malaria may still occur, so malaria must always be considered in any patient with a febrile illness post-transfusion.
Subject(s)
Malaria/transmission , Transfusion Reaction , Animals , Antibodies, Protozoan/blood , Antigens, Protozoan/blood , Blood Donors , Donor Selection , Humans , Malaria/diagnosis , Malaria/prevention & control , Plasmodium/immunology , Plasmodium/isolation & purification , Risk Management , SafetyABSTRACT
BACKGROUND AND OBJECTIVES: Although uncommon, five cases of transfusion-transmitted malaria have been documented in England over the last 20 years. With the reappearance onto the market of high-quality malaria antibody assays, and by utilizing the results of analysis of these five cases, it has been possible to review the donor malaria-deferral guidelines. MATERIALS AND METHODS: Details of the five cases of post-transfusion malaria were reviewed against the proposed new donor-deferral guidelines for malaria. RESULTS: Three of the five cases of post-transfusion malaria were directly attributable to the deferral guidelines, allowing infectious donors to be bled. CONCLUSIONS: The proposed new guidelines will prevent further cases of transmission from semi-immune individuals.
Subject(s)
Blood Donors , Malaria/etiology , Transfusion Reaction , Antigens, Protozoan , Blood Banks , Blood-Borne Pathogens , Disease Transmission, Infectious , Donor Selection , England , Female , Humans , Malaria/blood , Malaria/diagnosis , Male , Middle Aged , Practice Guidelines as Topic , Risk , Travel , Tropical MedicineABSTRACT
A case of transfusion-transmitted malaria was identified in a 50-year-old male patient with sickle cell disease. The donor was Ghanaian, but had migrated to the UK some years previously and had not left the UK for 8 years. The donor met all of the extant donor selection guidelines [1] and a donation was consequently collected. However, on subsequent investigation of the case, the donor was found to be parasitaemic and have high titre malarial antibodies. As a result of this case, changes to the United Kingdom donor selection guidelines have been proposed. These changes will prevent any such further transmissions.
Subject(s)
Blood Transfusion/methods , Disease Transmission, Infectious/legislation & jurisprudence , Malaria, Falciparum/etiology , Malaria, Falciparum/transmission , Animals , Blood Donors , Blood-Borne Pathogens , Disease Transmission, Infectious/prevention & control , Female , Guidelines as Topic , Humans , Male , Plasmodium falciparum/immunology , Plasmodium falciparum/metabolism , Travel , United KingdomABSTRACT
BACKGROUND AND OBJECTIVES: The two key objectives of the study were, first, to evaluate the sensitivity and specificity of a recombinant antigen-based malarial enzyme-linked immunoassay (EIA) and, second, to estimate the risk associated with implementing this test with a shortened cellular component restriction period (6 months rather than the standard 12-36 months) for blood donors with a malarial risk exposure. MATERIALS AND METHODS: Blood donors were recruited into four distinct groups [non-exposed (control), malarial area 'visitors', 'residents' and 'previous infection') and screened by using the Newmarket malarial antibody EIA. Assay specificity was evaluated in unexposed blood donors, and sensitivity was determined in acute clinical samples. RESULTS: No parasitaemic donors were detected amongst 337 malarial 'visitors' who had returned from a malaria-endemic area less than 6 months previously, or for 402 'visitors' or 'residents' who had returned from a malaria-endemic area more than 6 months previously. The incidence of malarial antibodies within the exposed blood donor groups was 1.33% (10/751). In acute clinical non-donor samples, the Newmarket EIA detected 106/108 (98.1; 93.5-99.5%) 'film' positive Plasmodium falciparum infections and 12/12 (100, 75.7-100.0%) P. vivax infections. The estimated additional risk exposure of the proposed new strategy was one infectious P. falciparum donation per 175 years or 1 per 4.2 years for P. vivax. CONCLUSIONS: The study findings support the efficacy and safety of a targeted screening strategy combining antibody screening with a 6-month cellular component restriction period for donors with a declared malarial risk.
Subject(s)
Blood Donors , Immunoenzyme Techniques/standards , Malaria/diagnosis , Plasmodium falciparum/immunology , Algorithms , Animals , Antibodies, Protozoan , Humans , Incidence , Malaria/epidemiology , Mass Screening/methods , Mass Screening/standards , Risk Assessment , Sensitivity and Specificity , Time FactorsABSTRACT
The hormonal changes that take place in pregnancy cause breast tissue to proliferate and differentiate. Abortion interrupts this process and may leave the proliferated, undifferentiated breast tissue at higher risk of carcinogenesis. This review explains the supposed difference in effects of induced and spontaneous abortion upon the breast tissue and examines the literature for a link with breast cancer. Additional subcategories examined include parity, number of abortions, gestation, and maternal age at abortion. A comparison of retrospective and prospective studies is made and possible sources of bias are identified. There is no evidence to support a link between spontaneous abortion and breast cancer. Absence of a link with induced abortion is less clear, and further research should concentrate on investigating any relationship. We suggest that prospective research is used, with point of entry at first termination.