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Vast changes are taking place in vaccinology consequent to the introduction of new technologies. Amongst the vaccines included in the Expanded Programme of Immunization (EPI), the pertussis vaccine has been replaced by acellular purified fractions devoid of side-effects. Non-pathogenic but immunogenic mutants of tetanus and diptheria toxins are likely to replace the toxoids. An effective vaccine against hepatitis B prepared by recombinant technology is in large-scale use. Conjugated vaccines against Haemophilus influenzae b, S. pneumococcus and meningococcus are now available, as also vaccines against mumps, rubella and measles. Combination vaccines have been devised to limit the number of injections. Vaccine delivery systems have been developed to deliver multiple doses of the vaccine at a single contact point. A genetically-engineered oral vaccine for typhoid imparts better and longer duration of immunity. Oral vaccines for cholera and other enteric infections are under clinical trials. The nose as a route for immunization is showing promise for mucosal immunity and for anti-inflammatory experimental vaccines against multiple sclerosis and insulin-dependent diabetes mellitus. The range of vaccines has expanded to include pathogens resident in the body such as Helicobacter pylori (duodenal ulcer), S. mutans (dental caries), and human papilloma virus (carcinoma of the cervix). An important progress is the recognition that DNA alone can constitute the vaccines, inducing both humoral and cell-mediated immune responses. A large number of DNA vaccines have been made and shown interesting results in experimental animals. Live recombinant vaccines against rabies and rinderpest have proven to be highly effective for controlling these infections in the field, and those for AIDS are under clinical trial. Potent adjuvants have added to the efficacy of the vaccines. New technologies have emerged to 'humanize' mouse monoclonals by genetic engineering and express these efficiently in plants. These recombinant antibodies are opening out an era of highly specific and safe therapeutic interventions. Human recombinant antibodies would be invaluable for treating patients with terminal tetanus and rabies. Antibodies are already in use for treatment of cancer, rheumatoid arthritis and allergies. An advantage of preformed antibodies directed at a defined target and given in adequate amounts is the certainty of efficacy in every recipient, in contrast to vaccines, where the quality and quantum of immune response varies from individual to individual.
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PMID:The impact of new technologies on vaccines. 1073 30

The adverse effects of vaccines include local reactions and systemic symptoms or illnesses. Local reactions are frequent, most often presenting as transient pain, redness, edema and/or nodule. Fever of short duration is the main systemic symptom, generally occurring within 24-48 hours following vaccination. Some vaccines have recognized specific adverse effects such as thrombocytopenic purpura for the measles-mumps-rubella vaccine, and febrile convulsions for the pertussis vaccine. Hepatitis B vaccine and Haemophilus influenzae type b vaccine have been respectively suspected to be responsible for neurological demyelinating disease and insulin-dependent diabetes mellitus, but large-scale epidemiological studies have failed to confirm these allegations.
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PMID:[Secondary effects of vaccinations]. 1127 Feb 59

Women with transfusion dependent thalassaemia suffer from failure of pubertal growth and delayed onset of menarche with amenorrhea, anovulation and infertility. With improved pediatric and hematological care is now possible, for patients with b thalassaemia, to achieve a pregnancy. Pre-pregnancy assessment included checks for hypothyroidism and diabetes, for hepatitis B and C, human immunodeficiency virus, Rubella, cardiac functions, liver functions by estimating aspartate and alanine aminotransferases, gamma-glutamyl transpeptidase, alkaline phospatase, and total plasma proteins. The frequency of blood transfusion needed to be increased in order to maintain the hemoglobin concentration above 10 g/dl. Desferroxamine must be stopped as soon as pregnancy is diagnosed continuing the administration of the folic acid supplements throughout pregnancy. Desferroxamine will be resumed after delivery. The safety of iron chelation with desferroxamine during the periconceptional period and pregnancy has not yet been established. Some animal studies have shown skeletal anomalies; other published studies report seven women with b thalassaemia major who became pregnant while taking desferroxamine: all the women had normal babies. The mode of delivery is usually vaginal, while Cesarean section is performed in those cases with pre-eclampsia, fetal distress, cephalopelvic dysproportion, slow progression of labor, as in women without thalassaemia. In conclusion, with the advent of regular blood transfusion associated with iron chelation therapy, pregnancy in b thalassaemia can be safe for mothers and their babies with appropriate care.
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PMID:[Pregnancy in women with thalassaemia]. 1139 93

Previous studies have suggested a relationship between reproductive history, pregnancy and birth factors, and the risk of neuroblastoma. We conducted a case-control telephone interview study that included a total of 504 children under the age of 19 years with newly diagnosed neuroblastoma identified by two national collaborative clinical trials groups, the Children's Cancer Group and the Pediatric Oncology Group. A total of 504 controls, matched to cases on age, were identified by random digit dialing. Conditional logistic regression was used to estimate the matched odds ratio (OR) and 95% confidence interval (CI) with adjustment for household income, and maternal race and education. In addition, case subgroups defined by age at diagnosis, tumour MYCN oncogene amplification status, and stage were evaluated. A suggestive pattern of increased risk was seen for a greater number of prior pregnancies, history of previous miscarriages and induced abortions, with nearly a twofold increase in risk for two or more prior induced abortions (OR = 1.9, 95% CI [1.0,3.7]). No association was found for the following diseases or conditions during pregnancy: hepatitis, rubella, measles, mumps, chickenpox, mononucleosis, vaccinations, morning sickness, pre-eclampsia, bleeding, proteinuria, anaemia, urinary tract infections, heart disease, kidney disease, liver disease and diabetes. A weak association was found for hypertension during pregnancy. Several labour and delivery factors were related to an increased risk, including threatened miscarriage, anaesthetic during labour (specifically epidural) and caesarean delivery. We found associations between premature delivery (<33 weeks: OR = 1.9, 95% CI [0.7,4.8]), very low birthweight (<1500 g: OR = 2.6, 95% CI [0.7,10.3]) and risk of neuroblastoma. There was no consistent pattern of increased risk found for most factors within subgroups defined by age at diagnosis, stage or MYCN status.
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PMID:Association of pregnancy history and birth characteristics with neuroblastoma: a report from the Children's Cancer Group and the Pediatric Oncology Group. 1170 80

Appropriate preconception health care improves pregnancy outcomes. When started at least one month before conception, folic acid supplements can prevent neural tube defects. Targeted genetic screening and counseling should be offered on the basis of age, ethnic background, or family history. Before conception, women should be screened for human immunodeficiency virus and syphilis infection and begin treatment to prevent the transmission of disease to the fetus. Immunizations against hepatitis B, rubella, and varicella should be completed, if needed. Women should be counseled on ways to prevent infection with toxoplasmosis, cytomegalovirus, and parvovirus B19. Environmental toxins such as cigarette smoke, alcohol, and street drugs, and chemicals such as solvents and pesticides should be avoided. In women with diabetes, it is important to optimize disease control through intensive management before pregnancy. Medications for hypertension, epilepsy, thromboembolism, depression, and anxiety should be reviewed and changed, if necessary, before the patient becomes pregnant. Counseling about exercise, obesity, nutritional deficiencies, and the overuse of vitamins A and D is beneficial. Physicians may also choose to discuss occupational and financial issues related to pregnancy and to screen patients for domestic violence.
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PMID:Preconception health care. 1261 25

Viruses have long been considered a major environmental factor in the aetiology of Type I (insulin-dependent) diabetes mellitus and recent work has greatly confirmed and extended this role. In addition to the enteroviruses, there are several other viruses which, from time to time, have been considered potential causal agents for human diabetes. With the exception of rubella, their role is not clear. The relation of enteroviruses with Type I diabetes has only been properly clarified by the use of new technologies, especially those based on polymerase chain reaction methods to identify them in blood. It is now evident from studies in several countries that enterovirus infection accompanies or precedes the onset of diabetes in many children. It is less certain whether this is true for older persons or for other types of diabetes. Enterovirus infection in pregnancy has also been suggested to cause diabetes in children. The infection with enteroviruses seems to be linked to the induction of islet-cell autoantibodies as well as to the expression of interferon-alpha. Both of these events are connected with islet-cell destruction. It has become increasingly important to establish the nature of the infecting virus in the early stages of diabetes. It seems likely that a number of viruses of the coxsackie or echovirus type are involved, although the nature of the nucleotide sequences responsible for diabetogenicity remains elusive.
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PMID:The role of viruses in human diabetes. 1237 75

Type 1 diabetes (T1D) results from the destruction of pancreatic beta cells. Genetic factors are believed to be a major component for the development of T1D, but the concordance rate for the development of diabetes in identical twins is only about 40%, suggesting that nongenetic factors play an important role in the expression of the disease. Viruses are one environmental factor that is implicated in the pathogenesis of T1D. To date, 14 different viruses have been reported to be associated with the development of T1D in humans and animal models. Viruses may be involved in the pathogenesis of T1D in at least two distinct ways: by inducing beta cell-specific autoimmunity, with or without infection of the beta cells, [e.g. Kilham rat virus (KRV)] and by cytolytic infection and destruction of the beta cells (e.g. encephalomyocarditis virus in mice). With respect to virus-mediated autoimmunity, retrovirus, reovirus, KRV, bovine viral diarrhoea-mucosal disease virus, mumps virus, rubella virus, cytomegalovirus and Epstein-Barr virus (EBV) are discussed. With respect to the destruction of beta cells by cytolytic infection, encephalomyocarditis virus, mengovirus and Coxsackie B viruses are discussed. In addition, a review of transgenic animal models for virus-induced autoimmune diabetes is included, particularly with regard to lymphocytic choriomeningitis virus, influenza viral proteins and the Epstein-Barr viral receptor. Finally, the prevention of autoimmune diabetes by infection of viruses such as lymphocytic choriomeningitis virus is discussed.
Diabetes Metab Res Rev
PMID:A new look at viruses in type 1 diabetes. 1259 41

The congenital rubella syndrome (CRS) is associated with increased risk for diabetes and thyroid disease. However, the mechanisms by which the rubella virus may cause these diseases are poorly characterized. Previous studies were carried out before modern immunological methods were available. The present study aimed at evaluating whether autoimmune mechanisms are involved in the pathogenesis by analysing antibodies to biochemically characterized autoantigens. The incidence of clinical diabetes, thyroid disease, coeliac disease and related antibodies (islet cell antibodies, ICA; insulin autoantibodies, IAA; antibodies to the tyrosine phosphatase related IA-2 molecule, IA-2 A and glutamic acid decarboxylase, GADA; thyroid peroxidase, TPO; tissue transglutaminase, TTGA; and gliadin, AGA) and HLA risk genotypes were analysed in 37 subjects affected by or exposed to rubella during fetal life (mean age 22.5 years). One patient had diabetes and four patients had clinical hypothyroidism at the time of the examination. ICA, IAA, GADA or IA-2 A were not detected in any of the patients, while five patients tested positive for TPO antibodies. Coeliac disease or TTGA were not observed. Eight patients carried the HLA-DR3-associated HLA-DQB1*02-DQA1*05 haplotype. These results provide no evidence of an increased frequency of markers for humoral beta-cell autoimmunity in patients with CRS suggesting that diabetes in CRS may be caused by other than autoimmune mechanisms.
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PMID:Humoral beta-cell autoimmunity is rare in patients with the congenital rubella syndrome. 1293 Mar 64

Vaccinations protect to a high degree against infectious diseases, but may cause side effects. In the Netherlands since 1962 the adverse events following immunizations are registered and analysed by the National Institute of Health and Environment (RIVM). Since 1983 a permanent Committee of the Dutch Health Council reviews adverse events reported to the RIVM. With the so-called killed vaccines the side effects are mainly local (redness, swelling, pain) or general (fever, listlessness, irritability, sleep and eating problems). They are seen mainly after DPT-IPV vaccination against diphtheria, pertussis, tetanus and poliomyelitis. Some side effects occur rarely (collapse reactions, discoloured legs, persistent screaming and convulsions) and very rarely serious neurological events are reported. After MMR vaccination against measles, mumps and rubella, cases of arthritis, thrombocytopenia and ataxia are reported sporadically. Usually, they have a spontaneous recovery. During recent years a scala of diseases or symptoms have been associated with vaccination (presumed side effects). Careful and extensive investigations have shown that such hypotheses could not be supported. Examples are allergic diseases as asthma, diabetes mellitus, multiple sclerosis (after hepatitis B vaccination), autism and inflammatory bowel disease (after MMR vaccination) and sudden infant death syndrome. The total number of cases where at least a possible relation between side effects and vaccination is observed--apart from local reactions and moderate general symptoms--is very rare (about 0.25 per 1000 vaccinations) and does not balance the benefits from vaccination. There appears increasing doubt about the use and safety of vaccinations. More research is needed about the motives of people to choose for and against vaccination. The education about vaccination for parents and professionals who are involved with vaccination has to be improved. Internet can play an important role.
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PMID:[Childhood vaccinations anno 2004. II. The real and presumed side effects of vaccination]. 1503 89

The genetic disorders are chronic in nature and, therefore, require continuous support and health care. Consequently, the genetic diseases cause formidable economic and psychosocial burdens on the family with negative reflection on the community at large. The genetic diseases are a heterogeneous group that result in varieties of chronic health ailment as a result of defects in the genetic material. The congenital malformations and some genetic defects may result from exposure to radiation, pharmaceutical drugs, the exposure of the mother during pregnancy to certain infectious diseases, such as rubella, toxoplasma or viruses. It may also result as a side effect of chronic diseases, including diabetes, hypertension or varieties of environmental factors, or both. The other group of genetic diseases are transmitted from parents to the offspring through a specific pattern of inheritance exemplified by recessive genetic disorders. This group includes the sickle cell gene, the thalassemias, the hemophilias, inborn errors of metabolism and red cell enzymopathies. The main etiological factors of genetic diseases and congenital malformations are 1) Genetic defects which are transmitted to offspring through carriers of affected parents. 2) Mutations in the genetic materials due to spontaneous mutations, exposure of the mother during pregnancy to infectious diseases, such as rubella and toxoplasma, receiving certain teratogenic drugs during pregnancy, exposure of the mother to ionizing radiation during pregnancy such as x-ray and chronic diseases of the mother, such as diabetes mellitus. 3) Others such as difficult labor or injury to the baby, during or after labor. This paper reviews the natural history of common blood genetic disorders and the means of prevention and control, focusing on pre-marital screening as a means of prevention.
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PMID:The natural history and the national pre-marital screening program in Saudi Arabia. 1557 76


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