In view of the risk of introduction of yellow fever into South-East Asia, comparative studies have been made of yellow fever vaccination in Malayan volunteers with a high prevalence of antibody to related viruses and in volunteers without related antibody. In a previous paper the neutralizing antibody responses of these volunteers were reported. The present paper describes the haemagglutinin-inhibiting (HI) antibody responses of the same groups of volunteers and discusses the relationship of these responses to the neutralizing antibody responses.The HI responses to yellow fever following vaccination closely paralleled the neutralizing antibody responses whether vaccination was subcutaneous or by multiple puncture. Volunteers with a high level of YF HI antibody due to infection with other group B viruses were found to be less likely to show a significant YF HI response than those without antibody. 90% of HI responses could be detected by the 21st day after vaccination.As with neutralizing antibody responses, volunteers given vaccine doses of 50-500 mouse intracerebral LD(50) subcutaneously gave greater responses than those given higher doses.
Studies have recently been published of surveys of antibodies to common respiratory viruses in human sera from several parts of the world. The present article reports the findings of a survey of antibodies to two more viruses (adenovirus type 8 and coxsackievirus type A21) in human sera mainly collected from six widely separated geographical regions (Alaska, England, Marshall Islands, Sarawak, South-West Africa and Tunisia).A world-wide geographical distribution of infection with these two viruses was found. However, antibodies to individual viruses were not found with the same frequency in all countries; and, in marked contrast to the findings in the earlier surveys of antibodies to the common respiratory viruses, the frequency of antibodies was not the same for each virus in sera from the same country. It was not possible to draw any final conclusions as to the reasons for the observed differences.
Epidemiological studies of human leptospirosis have generally been limited to countries with specialized laboratories employing the microscopic-agglutination (MA) test. The sensitized-erythrocyte-lysis (SEL) test is much simpler for routine hospital laboratories to carry out and it has been found valuable in the diagnosis of human leptospirosis. This paper reports the results of studies of the SEL test as an epidemiological tool in serological surveys.The results showed that the significant SEL titre was 1:80 and that the sensitivity of the test depended possibly on the antigen preparation and the amount of complement used. Most of the SEL antibodies were found to persist at significant titres for about 1 year after active infection, but less than half persisted longer than that. The SEL test is therefore useful for detecting recent infections and for indicating that stability of leptospirosis in an area.The endemicity of leptospirosis in West Malaysia was confirmed by the SEL test, based on the employment of 1:80 as the significant titre.
The passive transfer of convalescent sera did not protect the majority of mice against challenge with the homologous strain and was completely ineffective against challenge with strains unrelated by fluorescent antibody techniques. When the immune sera was incubated with the rickettsia in vitro and then inoculated into the mice a dramatic increase occurred in the number of surviving mice. The importance of these data in relation to published results with other species of rickettsia is discussed.
The immunomodulatory effects of morphine and the active components of marijuana, particularly tetrahydrocannabinol, on various aspects of the host immune parameters include alterations in humoral, cell-mediated and innate immunity. Most studies have shown immunosuppressive effects due to use of these abused substances, although there are reports that they may not produce any deleterious effect and may even enhance some aspects of host immunity. They reduce resistance to cancer growth and microbial pathogens in animals.
Rotaviral infections in cynomolgus monkeys (Macaca fasicularis) were studied to ascertain its suitability as a model of infection and diarrhea caused by group A human rotaviruses. Formula-fed monkeys were used as they could be observed closely. Experimental rotaviral infection of cynomolgus monkeys was age-dependent; only young monkeys were readily infected. Formula-fed newborns were readily infected with cell-culture-adapted human (WA) and simian (SA11) viruses and with a rotavirus from a human fecal specimen. However, diarrhea was detected only in very young animals. A number of rotaviral shedding patterns as a function of time were observed. Although there was no typical viral shedding pattern which represented exclusive association of viral infection with diarrhea, the initial level of viral excretion and the maximum level of viral shedding attained were much higher in animals with diarrhea. Seroconversion occurred in less than half of the inoculated animals. The presence of maternal rotaviral antibodies did not prevent infection or diarrhea.
Indirect ELISA shows that the antibodies to Calloselasma rhodostoma venom hemorrhagin (CR-HMG), thrombin-like enzyme (CR-TLE) and L-amino acid oxidase (CR-LAAO) exhibited strong to moderate cross-reactions with most crotalid and viperid venoms, but only anti-CR-LAAO cross-reacted with the elapid venoms. However, the indirect ELISA failed to detect some antigenic similarities demonstrable by cross-neutralization study. The double-sandwich ELISA for the three anti-C. rhodostoma venom components exhibited a much lower level of cross-reactions than the indirect ELISA.
Immunisation of health care workers and staff working in laboratory and hospital settings has been implemented since 1988. However due to the high cost of currently available HBV vaccine, many health personnel outside the Ministry of Health are not being immunised. This study sought to determine the immunogenicity of three doses of a low cost plasma-derived Korean HBV vaccine on employees of an institute for mentally handicapped and their spouses and children. We found that the Hepatitis B Vaccine-KGCC to be safe and immunogenic. The response to 10 mcg and 20 mcg Hepatitis B Vaccine-KGCC after third dose was good with 100% seroconversion.
Acquired haemophilia is a rare clinical condition arising from the spontaneous development of inhibitors to factor VIII. We describe two cases encountered in the University Hospital over the past five years. We also review the literature and discuss the therapeutic difficulties faced in dealing with patients with high levels of inhibitors. In one of these patients we also describe, for the first time in this region, a novel method in managing the acute bleeding episode in acquired haemophilia using recombinant factor VIIa.
A trial was conducted to compare the efficacy of intranasal vaccination in protecting goats against pneumonic pasteurellosis with intramuscular vaccination using an oil adjuvant vaccine, and a combination of the two methods. Forty goats were divided into four equal groups. Group 1 was vaccinated twice intranasally with formalin-killed Pasteurella haemolytica A2, group 2 was vaccinated twice intramuscularly with an oil adjuvant vaccine containing P haemolytica A7, and group 3 was initially vaccinated intranasally with the formalin-killed P haemolytica A2 followed by intramuscular vaccination with the oil adjuvant vaccine. In each group the two vaccinations were carried out four weeks apart. Group 4 was the unvaccinated control group. All goats were challenged intratracheally with 4 ml of an inoculum containing live P haemolytica A2 at a concentration of 1.3 x 10(7) colony forming units/ml two weeks after the last vaccination and were killed 14 days after the challenge. Although group 2 showed the highest clinical score following the challenge, deaths were observed only in group 3. Three goats in group 1 had pneumonic lung lesions, compared with six goats in group 2 and all the goats in groups 3 and 4. The lung lesions in group 1 were significantly (P < 0.05) less severe than in groups 3 and 4. Similarly, the lesions in group 2 were markedly less severe than in groups 3 and 4, although the differences were not significant. The difference between the extent of the lung lesions in the goats in groups 1 and 2 was not significant. Antibody against P haemolytica A2 in group 1 reached peak levels and was significantly (P < 0.01) higher than in the control group one week after the second vaccination, before declining.
The total and allergen-specific IgE response of patients with rhinitis, rhinoconjunctivities, rhinitis with asthma and rhinitis with dermatitis was analyzed to a panel of twelve high risk airborne and food allergens. It has been found that this panel will detect 96 percent of the allergen-causing diseases in children. It was found that 26 (76%) of the 34 young patients had a family history for atopy suggesting a high frequency of inheritance of allergic disorders. Elevated total IgE was found in most patients with allergic disease. Positive IgE antibody response to two species of Dermatophagoides mite-allergens was found in 7/12 (58%) patients with rhinitis, 11/11 (100%) patients with rhinoconjunctivitis, 7/9 (78%) cases ofrhinitis with asthma and 3/3 (100%) cases of rhinitis with dermatitis. Some of the patients also responded to food allergens. Food allergy was noted in 4/12 (33%) cases of rhinitis, 11/11 (100%) cases of rhinoconjunctivitis, 4/9 (44%) cases of rhinitis with asthma and 1/3 (33%) cases of rhinitis with dermatitis. Patients with rhinoconjunctivitis who tested positive at high titres for mites invariably had enhanced response for cockroaches, shrimps and crabs suggesting invertebrate antigen cross-reactivity. A few patients however, did not show this type of cross-reactivity although they had high titres of anti-mite IgE antibodies indicating that they responded to non cross-reacting allergen epitopes. Response to multiple allergens appears to be a common feature of most patients with respiratory or skin allergic diseases. The prevalence of multiple target-organ allergy to wide variety offood and environmental allergens complicates the long term management ofpatients with such allergic disorders.
Pseudorabies (Aujeszky's disease) is an economically significant disease of swine known to cause central nervous disorders, respiratory disease, reproductive failure and mortality in infected pigs. In attempts to eradicate the disease from becoming endemic, early detection is important to prevent further economic losses and to allow for detection and removal of infected pigs in domestic herds. Thus, a rapid and sensitive technique is necessary for the detection of the virus. For rapid and simple examination, an immuno - chromatographic lateral - flow assay system based on immunologic recognition of specific pseudorabies virus antigen was developed by utilising, as signal generator, colloidal gold conjugated to secondary antibody to detect primary or sample antibody in the sera of pseudorabies infected animals. The pseudorabies virus used as a capture antigen in the test strip was first cultivated in VERO cell culture and then purified by sucrose gradient separation to produce the viral protein concentration of 3.8 mg/ml. The standard pseudorabies antigens reacted well with the hyperimmune serum (HIS). The antibody detection system is basically composed of colloidal gold - labelled antibodies fixed on a conjugate pad, and the complementary pseudorabies antigen immobilised onto a nitrocellulose membrane forming capture zone. If the target antibody is present in a specimen, the colloidal gold-labelled antibody will form a complex with the antibody sample. Subsequently, the formed complex will migrate to the capture zone and is then bound to the solid phase via antigen - antibody interaction. As a result, a signal marker is generated by the accumulation of colloidal gold for detection confirmation. The results obtained demonstrated that the optimum combination of pseudorabies antigen needed as the capture reagent and gold conjugate as secondary antibody recognition marker was at a concentration of 0.38mg/ml and at 1:10 dilution factor respectively. The sensitivity of the solid - based test strip towards pseudorabies antibodies was high with a detection limit of 1 to 10,000 - dilution factor. The specificity of the assay was 100% with no cross - reaction being observed with other sera or antibodies. Accurate reading time needed for confirmation of the assay can be completed in 5 min with a whole blood sample of 25 microl. The colloidal gold - labelled antibody is stable at room temperature for 6 months or more (data not shown). Findings from this study indicated that the solid - based test strip assay system provided high sensitivity and specificity for the detection of pseudorabies at low levels of antibody concentration. The assay was rapid, simple, cheap, and does not require any sophisticated equipment. Thus, the solid based test strip will be a useful serological screening technique or for rapid diagnosis of an infectious disease in target populations of animals characterised by heterogeneous antibody responses.
A cucumber green mosaic mottle virus (CGMMV) full-length clone was developed for the expression of Hepatitis B surface antigen (HBsAg). The expression of the surface displayed HBsAg by the chimeric virus was confirmed through a double antibody sandwich ELISA. Assessment of the coat protein composition of the chimeric virus particles by SDS-PAGE analysis showed that 50% of the coat proteins were fused to the HBsAg. Biological activity of the expressed HBsAg was assessed through the stimulation of in vitro antibody production by cultured peripheral blood mononuclear cells (PBMC). PBMC that were cultured in the presence of the chimeric virus showed up to an approximately three-fold increase in the level of anti HBsAg immunoglobulin thus suggesting the possible use of this new chimeric virus as an effective Hepatitis B vaccine.
Malaysian infants would have to receive nine injections during the first few months of life in order to be protected against disease caused by hepatitis B (HBV), diphtheria, tetanus, pertussis and Haemophilus influenzae type b (Hib) if single HBV and Hib vaccines were used. We evaluated a combined DTPw-HBV/Hib vaccine administered at 1.5, 3 and 5 months after a birth dose of hepatitis B vaccine (HBV). One month after completion of the primary vaccination, 99% of subjects had seroprotective anti-HBV antibody levels, and at least 98% had seroprotective antibodies against diphtheria, tetanus, and Hib, and were seropositive for pertussis antibodies. The immune response to the combined vaccine was comparable to that induced by separate injections with DTPw, HBV and Hib vaccines. Overall, the DTPw-HBV/Hib vaccine was as well tolerated as separate administration of DTPw, HBV and Hib vaccines. The combined DTPw-HBV/Hib vaccine induces protection against five diseases as recommended in the Malaysian routine vaccination schedule. Use of the combined DTPw-HBV/Hib vaccine can reduce the required number of injections from nine to four in the first few months of life.
In recent years, Spirulina has gained more and more attention from medical scientists as a nutraceutical and a source of potential pharmaceuticals. The present study was conducted to elucidate the immunomodulatory effect of Spirulina fusiformis (a cyanobacterium of the family Oscillatoriaceae) in vivo and in vitro. The in vivo effect of S. fusiformis (400 or 800 mg/kg body wt.) on humoral immune response, cell-mediated immune response and tumour necrosis factor alpha was investigated in mice. We also evaluated the effect of S. fusiformis (50 or 100 microg/ml) in vitro on mitogen (phytohaemagglutinin)-induced T lymphocyte proliferation in heparinized human peripheral blood. For comparison, dexamethasone was used as a standard. In mice, S. fusiformis (400 or 800 mg/kg body wt.) administration significantly inhibited the humoral immune response, cell-mediated immune response (delayed-type hypersensitivity reaction (DTH)) and tumour necrosis factor alpha in a dose-dependent manner. In vitro, S. fusiformis (50 or 100 microg/ml) decreased the mitogen (phytohaemagglutinin)-induced T lymphocyte proliferation in a concentration-dependent manner when compared with control cells. These observations clearly suggest that S. fusiformis has a remarkable immunosuppressive effect, which provides a scientific validation for the popular use of this drug, and helped us in further work on investigating its complete mechanism of action.
A double blind, randomized, controlled Phase 2 clinical trial was conducted to assess the safety, immunogenicity, and biologic impact of the vaccine candidate Apical Membrane Antigen 1-Combination 1 (AMA1-C1), adjuvanted with Alhydrogel. Participants were healthy children 2-3 years old living in or near the village of Bancoumana, Mali. A total of 300 children received either the study vaccine or the comparator. No impact of vaccination was seen on the primary endpoint, the frequency of parasitemia measured as episodes >3000/microL/day at risk. There was a negative impact of vaccination on the hemoglobin level during clinical malaria, and mean incidence of hemoglobin <8.5 g/dL, in the direction of lower hemoglobin in the children who received AMA1-C1, although these differences were not significant after correction for multiple tests. These differences were not seen in the second year of transmission.