Immune-checkpoint gene expression and BCG response in non-muscle invasive bladder cancer.

METHODS: One-hundred-six patients diagnosed with non-muscle invasive bladder cancer and treated with intravesical BCG were included and divided into two groups, BCG-responsive (n = 47) and -unresponsive (n = 59). Immunohistochemistry was used to evaluate PD-L1 expression and MSI was assessed by a commercial multiplex PCR kit. The mRNA expression profile of 15 immune checkpoints was performed using the nCounter technology. For in silico validation, two distinct cohorts sourced from the Gene Expression Omnibus (GEO) database were used. RESULTS: Among the 106 patients, only one (<1 %) exhibited MSI instability. PD-L1 expression was present in 9.4 % of cases, and no association was found with BCG-responsive status. We found low gene expression of canonic actionable immune checkpoints PDCD1 (PD-1), CD274 (PD-L1), and CTLA4, while high expression was observed for CD276 (B7-H3), CD47, TNFRSF14, IDO1 and PVR (CD155) genes. High IDO1 expression levels was associated with worst overall survival. The PDCD1, CTLA4 and TNFRSF14 expression levels were associated with BCG responsiveness, whereas TIGIT and CD276 were associated with unresponsiveness. Finally, CD276 was validated in silico cohorts. CONCLUSION: In NMIBC, MSI is rare and PD-L1 expression is present in a small subset of cases. Expression levels of PDCD1, CTLA4, TNFRSF14, TIGIT and CD276 could constitute predictive biomarkers of BCG responsiveness.

Prevalência de imunidade à hepatite B entre profissionais de enfermagem atuantes em hemodiálise / Prevalencia de inmunidad a la hepatitis B entre enfermería profesional activa en la hemodiálisis / Prevalence of immunity to hepatitis B among professional nursing active in hemodialysis

Objective: to evaluate the prevalence of immunity to hepatitis B among nurses active on hemodialysis. Methods: Cross-sectional study was conducted with 63 professionals from a hemodialysis private service and 29 public service ones that answered a questionnaire containing information on demographics, labor, adoption of biosecurity measures in hemodialysis and related to vaccination, immunity and occupational exposure and non-occupational at Hepatitis B vírus. Results: Among the professionals from the private service, the prevalence of immunity to hepatitis B was 93.7% and among the professionals in the public service, the prevalence was 86.2%; in both services were not found statistically significant differences when characteristics related to demographics, laboral and occupational and non-occupational exposure to hepatitis B were considered. Conclusion: Possibly these high prevalences were due to complete immunization schedule against hepatitis B found in over 80% of study participants.

Objetivo: avaliar a prevalência de imunidade à hepatite B entre profissionais de enfermagem atuantes em hemodiálise. Métodos: Estudo seccional desenvolvido com 63 profissionais de um serviço privado de hemodiálise e 29 de um serviço público que responderam um questionário contendo informações demográficas, trabalhistas, sobre adoção de medidas de biossegurança em hemodiálise e relativas à vacinação, imunidade e exposição ocupacional e não ocupacional ao vírus da hepatite B. Resultados: Entre os profissionais do serviço privado, a prevalência de imunidade à hepatite B foi de 93,7% e, entre os profissionais do serviço público, a prevalência foi de 86,2%; em ambos serviços diferenças estatisticamente significativas não foram encontradas quando características demográficas, trabalhistas e de exposição ocupacional e não ocupacional ao vírus da hepatite B foram consideradas. Conclusão: Possivelmente essas elevadas prevalências se deviam ao esquema vacinal completo contra a hepatite B encontrado em mais de 80% dos profissionais de enfermagem participantes do estudo.

Objetivo: evaluar la prevalencia de inmunidad a la hepatitis B entre los profesionales de enfermería que trabajan en hemodiálisis. Métodos: Estudio transversal con 63 profesionales de servicio privado y 29 de servicio público que respondieron un cuestionario que contiene información demográfica, laboral, sobre la adopción de medidas de bioseguridad en hemodiálises, relacionados con la vacunación, la inmunidad, la exposición ocupacional y no ocupacional al virus de la hepatitis B. Resultados: Entre los profesionales del servicio privado, la prevalencia de la inmunidad a la hepatitis B fue 93,7% y entre los profesionales del público, la prevalencia fue de 86,2%; en ambos no se encontraron diferencias estadísticamente significativas cuando se consideraron los datos demográficos, laboral, exposición ocupacional y no ocupacional a la hepatitis B. Conclusión: Posiblemente estas elevadas prevalencias se debieron a el completo esquema de vacunación contra la hepatitis B que se encontró en más del 80% de los participantes del estudio.

Candidatos vacunales contra Mycobacterium tuberculosis: una actualización del tema / Mycobacterium tuberculosis vaccine candidates: an update on the topic

Fundamento: la eficacia protectora de la actual vacuna contra la tuberculosis, sirve para contrarrestar las formas pulmonares de esta enfermedad, su reactivación resulta variable o poco eficiente, lo cual impone la búsqueda urgente de nuevas alternativas profilácticas contra la enfermedad. El avance en la obtención de vacunas y de nuevas drogas más efectivas, depende en gran medida del conocimiento de las características del microorganismo, así como la respuesta del sistema inmune en función del agente patógeno. Objetivo: realizar una revisión actualizada en bases de datos médicas sobre los candidatos vacunales contra Mycobacterium tuberculosis. Métodos: se realizó una revisión bibliográfica acerca del tema de un total de 60 artículos publicados en bases de datos médicas, se escogieron 38 artículos correspondientes a la última década para conformar la investigación. Se mostraron los temas más usados referentes al agente patógeno, Mycobacterium tuberculosis, candidato vacunal y los mecanismos de acción sobre el sistema inmune. Se profundizó sobre los tipos de vacunas y las potencialidades terapéuticas específicas para el Mycobacterium tuberculosis, además de evaluar la implicación inmunológica con relación al candidato vacunal. Conclusiones: la simulación de la infección y los eventos inmunes que le suceden en el establecimiento de la inmunidad natural sin causar la enfermedad, son condiciones esenciales de una vacuna clásica.

Background: The tuberculosis constitutes a serious sanitary problem. The vaccination is a powerful method to prevent the infections. The effectiveness protector of the current vaccine against the tuberculosis, to counteract the lung forms of this illness and its reactivation, is variable or not very efficient, that which imposes the urgent search of new alternative prophylaxes against this illness. The advance in the obtaining of bovine and of new more effective drugs, it depends in great measure of the knowledge of the characteristics of the microorganism as well as the answer of the immune system in the pathogen agent's function. Objectives: to carry out an up-to-date revision on the Candidates vaccinates them against Mycobacterium tuberculosis. Methods: you real it hoisted a bibliographical revision of a total of 60 published articles, of them 40 articles corresponding to the last decade were chosen to conform the investigation. The relating more used topics were shown to pathogen agent Mycobacterium tuberculosis candidate vacunal and the mechanisms of action on the immune system. It was deepened on the types of vaccine and the therapeutic potentialities, specific for the M. tuberculosis, besides, to evaluate the immunologic implication with relationship to the candidate vacunal. Conclusions: The simulation of the infection and the immune events that happen him in the establish ment of the natural immunity, without causing the illness are essential conditions of a classic vaccine.

Innate immune response and acquired immune response in patients with chronic HBV infection / 临床肝胆病杂志

After the infection with HBV, the host′s antiviral immune response is a key factor for the outcome of infection. At present, it is widely believed that the host′s innate immunity and acquired immunity are impaired during chronic HBV infection, because of which HBV clearance cannot be achieved. To achieve a long-lasting immune control of HBV infection, we need to comprehensively understand the mechanisms of dysfunction of innate immune response and specific immune response in chronic HBV infection. This article summarizes the research advances in the immune response mechanism of chronicity of HBV infection.

Immune -mediated liver failure / 临床肝胆病杂志

The primary causative factors of liver failure include direct damage and immune -mediated liver injury.Increasing evidence sug-gests that immune -mediated injury plays a pivotal role in the pathogenesis of liver failure.The new concepts concerning the mechanisms of immune -mediated liver injury in liver failure are reviewed with relevant basic and clinical studies in both humans and animals.The innate and adaptive immunity,particularly the interaction of various immune cells and molecules,as well as apoptosis -related molecules,are dis-cussed in detail.

Comparative study of cardiac muscle structure between two models of chronic cor pulmonale induced by hypoxia and active immunization of M2-muscarinic receptor / 中华老年医学杂志

Objective To compare the similarities and differences in changes of cardiac muscle structure between the rat models of chronic cor pulmonale induced by hypoxia and active immunization of M2-muscarinic receptor under light microscope and electron microscope, and to explore the dependablity of the antibody effects on cardiac architecture. Methods The 48 healthy male Wistar rats were randomly divided into 4 groups: (1) Hypoxia group: the typical model of chronic cor pulmonale was established according to XUE's method; (2) Active immunization group was immunized by M2-muscarinic receptor peptide; (3) Control group was fed in normal condition; (4) Cyclosporin A group: the hypoxia group plus cyclosporin A treatment at the same time. The antibody against M2-muscarinic receptor was detected by SA-ELISA, and the pathological exemplar of cardiac muscle was observed by light microscope and transmission electron microscope. Results (1) Antibody level of M2-muscarinic receptor; the P/N values gradually increased along with the process of experiment, and the max value in active immunization group was 5. 13. At the end of the second week, the value in hypoxia group increased to 2.08, but was still less than in active immunization group (4.66). (2) Under light microscope: in hypoxia group and active immunization group, the hearts displayed significant alterations including disorder of cardiac muscle fiber, necrosis of myocardial cells together with the infiltration of inflammatory cells. There were no differences in light microscopic findings between hypoxia and cyclosporin A group. (3) Under transmission electronic microscope examination in both active immunization group and hypoxia group, the hearts showed s1imilar significant alterations such as focal cardiac muscle fiberlysis, loss of normal muscle fiber banding pattern, mitochondrial swelling and condensation, sarcoplasmic vacuolation and deposition of dense granules in both the sarcoplasmic and muscle fiber. The contour of myocyte was irregular and plasma membranes were discontinuous in some cells. All altered myocytes were fairly widely distributed throughout the myocardium. The interstitium showed edema, deposits of flocculent serum protein, activated fibroblasts and increased amounts of collagen fibers. No obvious alterations were observed in cyclosporin A group. Conclusions The positive rate and the titer of antibody against M2-muscarinic receptor are obviously increased in the rat model of chronic cor pulmonale, which indicates that there is a relationship between the antibody against M2-muscarinic receptor and the pathogenesis of chronic cor pulmonale.

Iron chelator inducesMIP-3alpha/CCL20 in human intestinal epithelial cells: implication for triggeringmucosal adaptive immunity

A previous report by this laboratory demonstrated that bacterial iron chelator (siderophore) triggers inflammatory signals, including the production of CXC chemokine IL-8, in human intestinal epithelial cells (IECs). Microarray-based gene expression profiling revealed that iron chelator also induces macrophage inflammatory protein 3 alpha (MIP-3alpha)/ CC chemokine-ligand 20 (CCL20). As CCL20 is chemotactic for the cells involved in host adaptive immunity, this suggests that iron chelator may stimulate IECs to have the capacity to link mucosal innate and adaptive immunity. The basal medium from iron chelator deferoxamine (DFO)-treated HT-29 monolayers was as chemotactic as recombinant human CCL20 at equivalent concentrations to attract CCR6+ cells. The increase of CCL20 protein secretion appeared to correspond to that of CCL20 mRNA levels, as determined by real-time quantitative RT-PCR. The efficacy of DFO at inducing CCL20 mRNA was also observed in human PBMCs and in THP-1 cells, but not in human umbilical vein endothelial cells. Interestingly, unlike other proinflammatory cytokines, such as TNF-alpha and IL-1beta, a time-dependent experiment revealed that DFO slowly induces CCL20, suggesting a novel mechanism of action. A pharmacologic study also revealed that multiple signaling pathways are differentially involved in CCL20 production by DFO, while some of those pathways are not involved in TNF-alpha-induced CCL20 production. Collectively, these results demonstrate that, in addition to some bacterial products known to induce host adaptive immune responses, direct chelation of host iron by infected bacteria may also contribute to the initiation of host adaptive immunity in the intestinal mucosa.

Prevalence of rubella antibodies among schoolgirls in Sana'a, Republic of Yemen

To determine the prevalence of rubella antibodies and age of exposure to rubella among Yemeni schoolgirls, we studied the sera samples of 323 female students [age range 11-21 years; mean age 16.26 +/- 1.89 years] drawn from three schools in Sana'a. All samples were screened for rubella IgG antibodies using enzyme linked immunosorbent assay and, if negative, for IgM in order to exclude the possibility of recent exposure. Of 323 sera, 296 [91.64%] were positive for rubella IgG. All IgG negative sera were also IgM negative. Comparable antibody prevalence was observed in all age groups. The prevalence of rubella IgG among Yemeni schoolgirls is high, with most becoming immune between the ages of 11 and 21 years. Although the age of exposure seems to be </= 13 years, further investigation is needed to confirm this

Study on the effect of mouse pregnancy immunological tolerance induced by oral antigen administration / 中华妇产科杂志

0 05) Conclusion The results suggested that pregnancy immunological tolerance can be induced efficiently and the ELR can be decreased significantly by oral administration of proper dosage antigens of OVA and TMA2

[Influence of helminthic infections and nutritional status on immune response in Venezuelan children]. / Influencia de las infecciones helmínticas y el estado nutricional en la respuesta inmunitaria de niños venezolanos.

We investigated the influence of nutritional status, as determined from anthropometric measurement, and of helminthic infections on the immune response of children of low socioeconomic status in two rural communities in Venezuela: El Cardón in the state of Nueva Esparta and San Daniel in the state of Miranda. A total of 125 boys and girls between 2 and 15 years old participated in the study. Their socioeconomic stratum was determined by a modified Graffar method. A physical examination was performed, as was also an anthropometric evaluation that took into account three indicators--weight-for-height, weight-for-age, and height-for-age--according to parameters established by the World Health Organization. Other examinations included feces, secretory IgA in saliva, total serum IgE, and anti-Ascaris-specific immunoglobulins. The children in both of the communities were in strata IV and V of the of Graffar scale, with a significantly greater number of stratum V inhabitants in San Daniel (P < 0.001). The results suggest that exposure level and individual susceptibility to the parasites are determining factors in parasitic infection and immune system behavior. The intensity of the parasitic burden plays an important role in stimulating polyclonal IgE, which diminishes the effectiveness of the specific response to those infections. On the other hand, nutritional deficiencies could change the immune mechanisms of the mucous membranes, negatively influence the synthesis of secretory IgA, and stimulate the production of polyclonal IgE. Poor sanitary and socioeconomic conditions promote more exposure to gastrointestinal parasites and a deficient nutritional status, which modulates the immune response and affects serum IgE and secretory IgA production mechanisms.

Impaired immune response to natural infection as a correlate of vaccine failure in a field trial of killed oral cholera vaccines.

In a field trial carried out in 1985 in Matlab, Bangladesh, the authors evaluated whether subjects who developed Vibrio cholerae 01 infections during the first year after earlier receipt of B subunit-killed whole cell (BS-WC) or killed whole cell-only (WC) oral cholera vaccines exhibited deficient serum vibriocidal immune responses to these infections. After severe V. cholerae 01 infections (n = 70) in subjects > 5 years of age, the age group in which both vaccines were efficacious, a 6.5 geometric mean-fold rise of serum vibriocidal antibodies was observed among vaccinees, compared with an 18.6 geometric mean-fold rise in placebo-recipients (p < 0.01). Depressions of serum vibriocidal responses among vaccinees were even more marked after asymptomatic infections (n = 30): a 1.1 geometric mean-fold rise in vaccinees versus a 5.9 geometric mean-fold rise in placebo-recipients (p < 0.01). The authors conclude that subjects who failed to be protected by BS-WC and WC, despite being in the age group for which these vaccines were protective, exhibited poor immune responses even to the vigorous stimulus of natural infection. These findings raise the possibility that immune hyporesponsiveness may limit the potential efficacy attainable by cholera vaccines in populations with endemic cholera.

PIP: Natural infections by Vibrio cholerae 01 are known to confer substantial protection against recurrent infections in populations where cholera is endemic. This suggests that it may one day be possible to develop a highly effective oral vaccine against cholera. It is, however, curious that cholera continues to occur into adulthood in populations which have endemic cholera. This phenomenon could be the result of an inability among some individuals in endemic populations to mount suitable immune responses to natural infections. If such immune hyporesponsiveness is truly at work, it may be an important barrier against the development and use of an effective oral cholera vaccine. The authors evaluated whether deficient immune responses to natural infection were associated with the risk of vaccine failure among recipients of killed oral cholera vaccines in a field trial in Bangladesh during 1985. Their findings support the hypothesis that immune hyporesponsiveness, even after the vigorous stimulus of natural infection, may have limited the protection conferred by the vaccines studied in the trial.

Immune activation is a dominant factor in the pathogenesis of African AIDS.

The AIDS epidemic in Africa is very different from the epidemic in the West. As suggested here by Zvi Bentwich, Alexander Kalinkovich and Ziva Weisman, this appears to be primarily a consequence of the over-activation of the immune system in the African population, owing to the extremely high prevalence of infections, particularly helminthic, in Africa. Such activation shifts the cytokine balance towards a T helper 0/2 (Th0/2)-type response, which makes the host more susceptible to infection with human immunodeficiency virus (HIV) and less able to cope with it.

PIP: The AIDS epidemic in Africa is very different from the epidemic in the West. Specifically, the following features of the AIDS epidemic in Africa distinguish it from the pattern of AIDS in North America and Europe: it is mainly a heterosexually transmitted disease with a male:female ratio of 1:1, and lacks the male homosexual and IV drug user risk groups; it is probably transmitted more easily; the progression of infection and disease is faster; and the clinical manifestations are different. This pattern of epidemic is also rapidly unfolding in Thailand, India, South America, and the Caribbean. Common to all regions in which this pattern dominates is the important role of prostitutes who comprise the major, initial reservoir of HIV from which it spreads into the general population as a sexually transmitted disease (STD). This pattern of spread has not, however, been found in the West or in other developed countries such as Japan, Australia, or New Zealand, where the prevalence of HIV infection among prostitutes remains low and is mostly associated with IV drug use. The widespread prevalence of STDs, the practice of scarification, transfusion, and the state of hygiene and nutrition in Africa may facilitate the transmission of HIV. The authors hypothesize, however, that the AIDS epidemics in the West and Africa are so different from each other because of a widespread altered background immune response among Africans. Infections, especially helminth infections, are endemic in Africa. Frequent exposure to these infections causes individual immune systems to be activated, or activated, thereby shifting the cytokine balance in such a manner which makes the host more susceptible to infection with HIV and less able to cope with it. Specifically, exposure to endemic infections has caused a shift away from an initial T1 helper cell response which would occur in the uninfected person to a less protective T helper 0/2-type response. Other types of immune activation have also taken place in the African population. This altered background immune response must be considered when designing vaccines and developing new therapies for HIV in Africa and other developing countries.

"Killer T-cells" give Gambian sex-workers the cutting-edge on HIV.

PIP: The results of a Gambian study may explain how 30 women out of 424 prostitutes in Nairobi, Kenya, remain uninfected with human immunodeficiency virus (HIV) after 5-6 years of prostitution, in spite of a prevalence rate of 90% in city sex workers. The Gambian study also found a group of uninfected sex workers who had been repeatedly exposed to the virus; researchers believe killer T-cells are responsible. Sarah Rowland-Jones of the Institute of Molecular Medicine at the University of Oxford, at the Medical Research Council's clinic in Fajara, Gambia, studied 6 female sex workers who had been prostitutes for more than 5 years and rarely practiced safe sex. Approximately 30% of sex workers in the region are infected with HIV; this suggests that the workers were exposed to the virus once or twice per month over 5 years. 3 of the women had high levels of killer T-cells; 2 had some level. Killer T-cells, or cytotoxic lymphocytes, seek out and destroy virus-infected cells; they are particularly effective against viruses (like HIV) which are passed cell to cell without passing through the bloodstream where they would be attacked by antibody. Although they are found in people with HIV, in most cases they are overwhelmed by the virus. One hypothesis in these uninfected cases is that the women were first infected with HIV-2, a less aggressive strain dominant in West Africa; built up an immunity to it; and then fought off the infection with HIV-1 that arrived later in Gambia. Rowland-Jones will next determine the levels of killer T-cells in the uninfected Nairobi sex workers; her results should be available in April 1995.^ieng

Efficacy of hepatitis B vaccine in the Gambian expanded programme on immunisation.

Because of the high prevalence of hepatitis B virus (HBV) infection in The Gambia, HBV vaccination has been incorporated into the national expanded programme on immunisation. We have assessed the efficacy of the vaccine against HBV infection and chronic carriage by examining 720 3-4-year-old children who had received the vaccine in infancy and 816 who had not received it. The vaccine was 84% (95% CI 78-89%) effective against infection and 94% (84-98%) effective against chronic carriage. Vaccinated infants of mothers positive for hepatitis B surface and e antigens were at greater risk of breakthrough infection and chronic carriage than infants of uninfected mothers. The high vaccine efficacy against the HBV carrier state, the main risk factor for the development of chronic liver disease and liver cancer, offers hope that the prevalence of these diseases may be reduced in the future.

PIP: As part of the Gambia Hepatitis Intervention Study, hepatitis B antigens and antibodies were assayed in 720 3-4 year old children who had received 4 doses of 10 mcg plasma-derived hepatitis B vaccine in infancy, the findings were compared with 816 controls. The cross sectional study took place from September, 1990, to July, 1991. Study subjects were tested for hepatitis B core antigen (HBcAg), as well as antigens and antibodies to hepatitis surface, e, and core protein, and those testing positive were tested a year later for HBsAg to determine chronic carrier status. Children negative for core antibody and surface antigen were considered uninfected; those positive for core antibody were considered infected; those positive for surface antigen 2 times 6 months apart were considered carriers. 4.6% of the vaccinated children were infected, and 0.6% were chronic carriers. 3 of these carriers had infected or carrier mothers, and 1 had only received 1 dose of vaccine. In the controls, there were 29% judged infected by anti-HBc, including 13% who were also positive for HBsAg. 86% of these were considered chronic carriers when tested a year later. Thus the vaccine was estimated to be 84% effective against infection and 94% effective against chronic carriage. The current Gambian vaccine consists of 2.5 mcg recombinant hepatitis B vaccine.

Antigenic and immunogenic sites of HIV-2 glycoproteins.

PIP: A new human retrovirus, HIV-2, serologically distinct from human immunodeficiency virus type 1 (HIV-1), was first reported in 1985 and isolated in 1986 from 2 AIDS patients from Guinea-Bissau and Cape Verde Islands. Findings related to the characterization of HIV-2 antigenic and immunogenic sites that stimulate strain and type-cross-reactive immunity are illustrated; data from preliminary studies of simian immunodeficiency virus (SIV) are presented; and epidemiological and biological characteristics of HIV-2 infection are also reviewed. Prevention of HIV-2 and SIVsm infection has been achieved in cynomolgus macaques by passive transfer of an anti-SIVsm serum pool with high antibody titres. The identification of antibody-binding regions of HIV is critical for vaccine development studies. The presence of highly immunogenic domains in the extracellular proteins of HIV-2 has also been demonstrated by Western blot analysis using bacterially expressed contiguous segments representing the HIV-2 envelope products. Over 95% of HIV-2 positive sera from Senegal reacted with these protein segments. The antibody-reactive peptide scanning method defined 8 distinct antibody-binding sites in the transmembrane protein gp36 of the HIV-2 strain ROD in addition to the highly immuno-dominant site present at the amino terminus of gp36. Antibody reactions of SIVm-infected macaque sera against selected SIVm envelope peptides were very similar to those of HIV-2 and HIV-1-infected human sera to the corresponding linear antigenic sites, indicating the existence of immunological parallelism between human and simian lentiviruses. HIV-2-induced immunity in inoculated macaques has been shown to protect against SIV-associated disease, indicating that the 2 viruses share group-specific protective immunity. In a study of human sera, the occurrence of an intertype cross-reacting V3-region-specific activity correlated with the presence of cross-neutralizing activity in sera. These findings indicate that the V3 region may be an important neutralizing site not only in HIV-1 but also in HIV-2.^ieng

BCG vaccination of full-term infants with chronic intrauterine malnutrition: influence of immunization age on development of post-vaccination, delayed tuberculin hypersensitivity.

To determine the effect of intrauterine growth retardation (IUGR) on the response to BCG vaccination, we evaluated the specific delayed tuberculin hypersensitivity of 57 full-term infants with symmetric IUGR (SGA or small for gestational age) and 52 full-term infants with normal intrauterine growth (AGA or appropriate for gestational age). The infants were evaluated using post-vaccination skin tests to tuberculin purified protein derivative (PPD) and tuberculin lymphocyte transformation tests. Using a positive response to the skin test as an indicator of delayed hypersensitivity, we found that the rate of response to BCG in the SGA and AGA groups was similar. A total of 65% of infants with IUGR responded to BCG vaccination. The response rate among SGA infants who were vaccinated at 5 days of age, about 26 days of age (weight > or = 2500 g), 3 months of age, and 6 months of age was 68%, 47%, 69%, and 88%, respectively. The overall response rate for infants with no IUGR was 71%; the rate response to BCG vaccination among this group was 52% (those vaccinated at 5 days of age), 90% (3 months of age), and 80% (6 months of age). Our data suggest that the immunogenicity of BCG vaccine is similar in term infants who have normal or abnormal intrauterine growth and the presence of IUGR should not be a reason for delaying BCG vaccination.

PIP: In Brazil, pediatricians followed 109 infants born at the University Hospital of Ribeirao Preto in Sao Paulo every 2 weeks for 3 months and then at 6 months to examine the effect of intrauterine growth retardation (IUGR) on the response to BCG vaccination. They used a tuberculin purified protein derivative to determine tuberculin hypersensitivity and a lymphocyte transformation test to determine lymphocyte proliferation to tuberculin 12-14 weeks after vaccination. The rate of response to BCG in the IUGR infants was basically the same as that of infants whose weight was appropriate for gestational age (AGA) (65% vs. 71%). Specifically, the rate among IUGR infants vaccinated at 5 days old, once they weighed at least 2500 gm (around 26 days old), 3 months old, and 6 months old was 68%, 47%, 69%, and 88%, respectively. The rate among AGA infants vaccinated at 5 days old, 3 months old, and 6 months old was 52%, 90%, and 80%, respectively. The results indicated that BCG vaccination was more immunogenic as the infants aged than when they were newborns, regardless of intrauterine status. They demonstrated that waiting to administer the BCG vaccination when the IUGR infants weighed 2500 gm had no advantage over administering the vaccination when they were newborns. In developing countries with a high prevalence of tuberculosis, such a delay would place these especially vulnerable infants at greater risk of tuberculosis.

Poliomyelitis case confirmation: characteristics for use by national eradication programmes.

Highly sensitive case definitions were first introduced by national poliomyelitis eradication programmes to avoid missing true cases of the disease, though false-positive diagnostic errors could still occur owing to low specificity. Extensive data from all 1620 cases of acute, flaccid paralysis reported in Brazil during 1987-88 provided an opportunity to study the characteristics of confirmed poliomyelitis cases and epidemiologically to evaluate potential case definitions that maximized both sensitivity and specificity. Cases that had been confirmed by wild poliomyelitis virus isolation were compared with those that had been rejected (non-polio cases). To guarantee the consistency of clinical, epidemiological and laboratory investigations, only cases less than 10 years of age that had been investigated within 15 days of the onset and with complete laboratory specimens were included. No single practical case definition combining both high sensitivity and high specificity emerged from the study. However, the results showed that poliomyelitis endemic countries with limited resources should give priority to the investigation of cases in less than 5-year-olds, cases with prodromal fever, cases without involvement in all four limbs, cases without progression greater than 3 days after the onset, and cases occurring in areas where poliomyelitis had recently been confirmed. In countries without laboratory resources, cases of acute, flaccid paralysis with initial involvement in one or both lower limbs and residual neurological sequelae at 60 days should be confirmed. Countries that are close to eradication may selectively reject any cases lacking laboratory confirmation, despite adequate specimen collection, if they do not have initial involvement in one or both lower limbs and residual neurological sequelae at 60 days.

PIP: In Sao Paulo, Brazil, physicians followed 85 full term, healthy, breast fed infants born between March 1986-September 1988 monthly for 1 year to compare their immunologic response to immunization with trivalent oral poliovirus vaccine (TOPV). They either received doses 1 day after birth and at 2, 4, and 9 months (group A) or at 2, 4, and 6 months (group B). They analyzed blood samples from the mother at childbirth, from the umbilical cord, and from the infant at 2, 4, 6, 9, and 12 months to measure poliovirus neutralizing antibodies. All but 1 infant had passively transferred antibodies at birth. Group A had higher polio antibodies during the 1st few months, greater seropositivity, and a lower proportion of susceptible infants than group B. In fact, at the end of 12 months, only 3.7% of infants in group A were susceptible to all 3 poliovirus types compared to 25.9% in group B. Seroconversion rates were considerably higher in group A infants from the 3rd dose forward (96.3-100%) than for those in group B (74.1-100%). The response for polioviruses 1 and 2 were essentially the same in both groups at 12 months (96.3-100%). The immunological response to poliovirus type 3 in group A was superior to that of group B at the end of 1 year (96.3% vs. 74.1%), however. Yet group B infants received their 1st dose of the vaccine at 2 months with a higher level of poliovirus 3 type (500,000 TCID50/dose) than group A infants received at birth (300,000 TCID50/dose). Thus immunization of newborns with TOPV provided more protection against polio than a higher vaccine concentration administered to infants beginning at months. This finding is especially relevant since polio type 3 was responsible for the polio outbreak in 1986 in northern Brazil.

Prevalence of Giardia lamblia antibodies in serum and milk in lactating women from different social classes in Egypt.

Prevalence and levels of systemic and milk antibodies to G. lamblia in the different social classes of the population were studied using the IFAT and nor-partigen immunoglobulin plates. Blood and milk samples were collected simultaneously from lactating women in urban (Cairo) and rural (Benha) areas. Serum IgG was present in 90% of rural low standard mothers, 58% of urban moderate standard mothers, and 25% or urban high standard mothers (P less than 0.01, P less than 0.001 and P less than 0.01). Antilog of mean of antibody titers was significantly higher in the low standard rural mothers than in the urban moderate and high standard ones. Specific secretory IgA antibody in milk was found in 71% of rural low standard mothers, 31% of urban moderate standard mothers, and 16.6% of urban high standard mothers (P less than 0.001, P less than 0.01 and P greater than 0.05). The antilog of mean S-IgA titers was also higher in the low standard rural mothers. The titer levels of S-IgA in the three classes did not show any correlation with the quantitative levels of total IgA in milk, while specific IgG showed a positive correlation with the total serum IgG in the low standard rural mothers only (P less than 0.05). This study documented the widely different antibody response to G. lamblia in individuals living in different social classes.

PIP: Total IgG and secretory IgA antibodies, and specific IgG and S-IgA antibodies against Giardia lamblia were assayed in serum and milk respectively from 118 Egyptian mothers. The women were selected from 3 social classes: 24 of upper class from Cleopatra Hospital, Cairo, 52 of moderate social class from Ain Shams Maternity Hospital, Cairo, and 42 of low social class from Maternal and Infant Welfare Centers in rural Benha. Total IgG and S-IgA antibodies were assayed with the nor-partigen method, and specific G. lamblia antibodies with an indirect fluorescent antibody method. IgG antibodies in serum specific for G. lamblia were present in 62.7% of the total group: 90% from the low, 58% of the moderate, and 25% of the high social groups, all significantly different. Mean total IgG levels were 15.42, 19.81 and 33.5 g/L in the 3 groups (n.s.). Secretory IgA antibodies specific for G. lamblia occurred in 42.3% of the total milk samples: in 71% of the low, 31% of the moderate, and 16.6% of the high social class groups (low group significantly different from moderate and high groups). The mean total IgA level in the milk samples did not differ from normal. While the specific IgG titers were positively correlated with the total IgG content in serum, milk total S-IgA levels were not significantly correlated with specific anti-Giardia lamblia S-IgA titers. These results were similar to those reported from other contexts, and support the advice that women breastfeed their infants through age 2 to confer immunity against Giardia parasites.

Hepatitis B surface and e antigen seropositivity in mothers and cord blood at Port Moresby General Hospital: implications for a control program.

Analysis of 100 unselected paired maternal and cord blood samples showed 11 mothers to be HBsAg positive and 6 of these to be also HBeAg positive. 5 cord blood samples were HBsAg positive and 3 were HBeAg positive. Assuming a protective efficacy rate of 75%, the present plasma-derived hepatitis B virus vaccine control program is likely to prevent the perinatal acquisition of the hepatitis B virus carrier state in 27 per 1000 children. The addition of immunoglobulin prophylaxis would be likely to reduce this by another 5 per 1000, but its use does not appear practicable at the present time.

PIP: 100 mother-infant pairs were tested for hepatitis B surface and e antigen and the results used to estimate effectiveness of the current vaccination program in Papua New Guinea. The 100 mothers and neonates born at the Port Moresby General Hospital in May-June 1990 were tested for HBsAg and HBeAg with the reversed passive hemagglutination technique (Green Cross Corp., Japan). 11 mothers were positive for HBsAg, and 6 of these for HBeAg. 5 cord bloods were positive for HBsAg, and 2 of these for HBeAg. 1 infant was positive for HBeAg only. All 3 infants positive for HBeAg were born of HBeAg mothers. It is assumed that HBsAg in infants is from passive transfer from the mother. HBeAg is indicative of a highly infectious state in a mother, and active infection in a newborn. It was calculated that the currently used plasma-derived vaccine, which has a protective efficacy rate (PER) of 75%, would be expected to protect 25/1000 children from becoming carriers, compared to 5/1000 more if immunoglobulin were given in addition. The higher costs of the new recombinant vaccine and of the plasma vaccine plus immunoglobulin were considered impractical.

The WHO Task Force on Vaccines for Fertility Regulation. Its formation, objectives and research activities.

Over the past 18 years, the WHO Task Force on Vaccines for Fertility Regulation has been supporting basic and clinical research on the development of birth control vaccines directed against the gametes or the preimplantation embryo. These studies have involved the use of advanced procedures in peptide chemistry, hybridoma technology and molecular genetics as well as the evaluation of a number of novel approaches in general vaccinology. As a result of this international, collaborative effort, a prototype anti-HCG vaccine is now undergoing clinical testing, raising the prospect that a totally new family planning method may be available before the end of the current decade.

PIP: The WHO Task Force on Vaccines for Fertility Regulation is one of several Task Forces, consisting of international, multidisciplinary groups of scientists and clinicians collaborating in research on specific goals, established in 1972. Its accomplishments are reviewed here. The Task Force convened a meeting in 1974 to select criteria for tissues and molecules capable of mounting antifertility responses. These molecules had to be restricted to the target tissue, sequestered in the reproductive tract, present transiently, and chemically characterized. Some of the antigens considered were sperm enzymes and membranes, as well as a data bank of sera naturally immunized against sperm. Other were anti-ovum and placenta molecules such as zona pellucida, the SP-1 placental antigen, and the placental hormones chorionic somatotrophin and human chorionic gonadotropin (hCH). Trophoblast-derived monoclonal antibodies and gene libraries are being screened. Anti-hCH is the vaccine composed of a portion of the beta subunit complexed to a carrier antigen, diphtheria toxoid, in a water- oil emulsion with an adjuvant has been tested in a phase I clinical trial in 1986-1988. A Phase II trial is being planned to see if the immune response in women is large enough to be capable of preventing pregnancy. Further improvements in the vaccine are being envisioned, such as incorporation of the peptide carrier conjugate and immune stimulant into biodegradable microspheres, hopefully to produce a longer-lasting immunity and a more stable vaccine. While the WHO Task Force on Vaccines for Fertility Regulation has been forced to cut back on some avenues of research, its success has stimulated other centers to take up several important projects, e.g. the sperm LDH and zona pellucida vaccines.