MEASLES ENCEPHALITIS—A Successful Method of Treatment with Typhoid Vaccine

During a 12-year period 50 patients with measles encephalitis were treated with typhoid vaccine—45 of them not until they were in a vegetative state. There were no deaths in the treated cases. All except one were clinically normal after treatment was ended. Late in the series it became apparent that after the clinical normal is attained and the electroencephalogram becomes normal, treatment should still be continued until the cortex has been “challenged” repeatedly and the electroencephalogram shown to remain normal.The “shock” element in the treatment with typhoid vaccine was prevented by anticipating and circumventing the unfavorable reactions to the vaccine.It may take 20 to 50 treatments or more with typhoid vaccine to return a patient to normality. Each individual is different and responds in a different period of time.     

莫西沙星治疗78例伤寒的临床疗效观察

目的：探讨莫西沙星在伤寒治疗中的临床意义。方法：将我院2008年6月至2010年6月期间78例确诊的伤寒患者随机分为治疗组（39例）和对照组（39例）,治疗组给予莫西沙星,对照组给予盐酸左氧氟沙星,均静脉滴注,每日1次,体温正常后7d停药。结粜：治疗组痊愈率94．8％,总有效率100％;对照组痊愈率92．3％,总有效率100％,两组痊愈率差异无统计学意义（P〈0．05）;治疗组开始退热和体温降至正常的时间均较对照组缩短,差异有显著意义（P〈0．05）。治疗组不良反应发生率明显低于对照组（P〈0．05）。结论：莫西沙星在伤寒治疗中具有疗效确切、无复发、副作用少等特点,在治疗非耐药和耐药伤寒中有重要作用,有较好的临床应用前景。     

莫西沙星治疗78 例伤寒的临床疗效观察

目的:探讨莫西沙星在伤寒治疗中的临床意义。方法:将我院2008年6月至2010年6月期间78例确诊的伤寒患者随机分为治疗组(39例)和对照组(39例),治疗组给予莫西沙星,对照组给予盐酸左氧氟沙星,均静脉滴注,每日1次,体温正常后7 d停药。结果:治疗组痊愈率94.8%,总有效率100%;对照组痊愈率92.3%,总有效率100%,两组痊愈率差异无统计学意义(P<0.05);治疗组开始退热和体温降至正常的时间均较对照组缩短,差异有显著意义(P<0.05)。治疗组不良反应发生率明显低于对照组(P<0.05)。结论:莫西沙星在伤寒治疗中具有疗效确切、无复发、副作用少等特点,在治疗非耐药和耐药伤寒中有重要作用,有较好的临床应用前景。     

Chloramphenicol Combined with Ampicillin in Treatment of Typhoid

Fifty out of 100 patients with typhoid fever, matched for age, stage of illness, and degree of fever, were treated with chloramphenicol and the other 50 were treated with chloramphenicol combined with ampicillin. The febrile period was shortened by up to 29% in patients treated with the combined drugs compared with those given only chloramphenicol. Moreover, no patient on combined therapy had a febrile relapse, whereas two relapses occurred among patients treated with chloramphenicol only. We conclude that chloramphenicol and ampicillin together are better than chloramphenicol alone in the treatment of typhoid fever.     

Immunological response of three mouse strains to typhoid vaccine and Vi antigen

Vi-agglutinin, active cutaneous anaphylaxis and protective responses (ed(50)) of three mouse strains (CFW, NIH, and Balb/cAnN) to acetone-inactivated typhoid vaccine and soluble Vi antigen were compared. Seven days after immunization with either typhoid vaccine or Vi antigen the three strains of mice differed with respect to Vi-antibody titers. Significant differences were observed in the protective responses. Each mouse strain was significantly better protected by the intraperitoneal than by subcutaneous route of immunization. Active cutaneous anaphylaxis was more pronounced in showing strain differences in response to Vi antigen. The serological responses to Vi antigen of the strains of mice did not correlate with their protective response.     

伤寒Vi多糖菌苗多糖含量及分子大小测定试验

伤寒Ｖｉ多糖菌苗是我国新近研制成功的一种多糖菌苗。为了严格控制该制品的质量,经反复试验,建立了多糖含量和分子大小的测定方法。本文报导了（１）用火箭电泳法测定伤寒Ｖｉ多糖菌苗多糖含量。经对不同实验条件进行比较,选择出较为理想的条件。用该法测定８批样品。结果均符合规程要求。对其中５批样品进行６次重复试验表明,该法的重复性好,操作简单,是测定多糖含量较为理想的方法。（２）用琼脂糖柱层析法对２８批伤寒Ｖｉ多糖菌苗的分子大小进行测定。对用该法所得柱层析收集液分别用Ｈｅｓｔｒｉｎ法和２０６ｎｍ扫描法测定其多糖回收率,对测定结果进行比较。结果表明,两种方法的测定结果无显著性差异（Ｐ＞０．０１）,而且重复性均好。可根据实验室条件选择测定方法。     

Stability of cholera and typhoid vaccines

Fluid plain and adsorbed and freeze-dried cholera and tyhpoid vaccines of different composition were examined for thermostability by potency testing (by active mouse protection tests) after exposure to 37 degrees C for 1, 2, 3, 4, 8 and 12 weeks. Loss of potency was evaluated by comparison with samples stored at 4 degrees C. The fluid plain cholera vaccine remained fully potent for 1--3 weeks, the adsorbed vaccine for at least 4 weeks. The fluid typhoid vaccines showed greater thermosensitivity than the fluid plain cholera vaccine. The freeze-dried cholera and typhoid vaccines were both very stable, retaining fully potency after at least 12 weeks' exposure to 37 degrees C. It should be emphasized that the above results apply exclusively to vaccines prepared by the methods used by the authors and formulated to identical compositions.     

Genetically determined differences in the response of alpha1-antitrypsin levels in human serum to typhoid vaccine

Summary Normal individuals and those homozygous and heterozygous for the gene which determines deficiency in serum ₁-antitrypsin (₁-at) were given an intravenous injection of typhoid vaccine. Following this injection the trypsin-inhibiting capacity of serum and the concentration of ₁-at increases markedly in normal individuals. Heterozygotes for the deficiency gene have an elevation of ₁-at and trypsin-inhibiting capacity of their serum but reach only 50 percent of the levels reached by homozygotes for the common gene (normal individuals). Their values are however temporarily in the range of normal men not given typhoid vaccine. Homozygotes for the deficiency gene show only a small elevation of ₁-at under these conditions. These findings demonstrate that (1) the increase in trypsin-inhibiting capacity of serum after an injection of typhoid vaccine is largely due to the elevation of the ₁-at concentration, and (2) the ₁-at deficiency gene inhibits the quantitative response of the ₁-at to such a stimulus.Supported in part by USPHS grant HE-06285 from the National Heart Institute.Some of these studies were carried out in the General Clinical Research Center Ward, U. C., FR-79, supported by the Division of Research Facilities and Resources, U.S. Public Health Service.     

伤寒Vi多糖菌苗接种反应观察

本文报告了对我国首次成功的伤寒Ｖｉ多糖菌苗进行人体接种反应观察结果,接种对象为２０至５４岁无伤寒病史,近年无伤寒菌苗接种史的健康人,共６０名,以完全随机的方法分为两组,实验组注射３０μｇＶｉ多糖菌苗,对照组注射Ｖｉ多糖菌苗的稀释液。其结果３０名Ｖｉ多糖菌苗接种者注射后体温无中重反应发生,局部红肿仅有１例中反应。注射后对血压、心律没有影响。红细胞计数,白细胞计数均在正常范围,与接种前相比,无显著差异     

Typhoid Outbreak in Songkhla,Thailand 2009–2011: Clinical Outcomes,Susceptibility Patterns,and Reliability of Serology Tests

Objective

To determine the clinical manifestations and outcomes, the reliability of Salmonella enterica serotype Typhi (S ser. Typhi) IgM and IgG rapid tests, and the susceptibility patterns and the response to treatment during the 2009–2011 typhoid outbreak in Songkhla province in Thailand.

Method

The medical records of children aged <15 years with S ser. Typhi bacteremia were analysed. The efficacy of the typhoid IgM and IgG rapid tests and susceptibility of the S ser. Typhi to the current main antibiotics used for typhoid (amoxicillin, ampicillin, cefotaxime, ceftriaxone, co-trimoxazole, and ciprofloxacin), were evaluated.

Results

S ser. Typhi bacteremia was found in 368 patients, and all isolated strains were susceptible to all 6 antimicrobials tested. Most of the patients were treated with ciprofloxacin for 7–14 days. The median time (IQR) of fever before treatment and duration of fever after treatment were 5 (4, 7) days and 4 (3, 5) days, respectively. Complications of ascites, lower respiratory symptoms, anemia (Hct <30%), and ileal perforation were found in 7, 7, 22, and 1 patients, respectively. None of the patients had recurrent infection or died. The sensitivities of the typhoid IgM and IgG tests were 58.3% and 25.6% respectively, and specificities were 74.1% and 50.5%, respectively.

Conclusion

Most of the patients were diagnosed at an early stage and treated with a good outcome. All S ser. Typhi strains were susceptible to standard first line antibiotic typhoid treatment. The typhoid IgM and IgG rapid tests had low sensitivity and moderate specificity.     

Head-to-Head Comparison of Humoral Immune Responses to Vi Capsular Polysaccharide and Salmonella Typhi Ty21a Typhoid Vaccines–A Randomized Trial

Background

The two typhoid vaccines, the parenteral Vi capsular polysaccharide and the oral live whole-cell Salmonella Typhi Ty21a vaccine, provide similar levels of protection in field trials. Sharing no antigens, they are thought to confer protection by different mechanisms. This is the first head-to-head study to compare the humoral immune responses to these two vaccines.

Methods

50 age- and gender-matched volunteers were immunized, 25 with the Vi and 25 with the Ty21a vaccine. Circulating plasmablasts reactive with whole-cell Salmonella Typhi or one of the typhoidal antigenic structures, Vi, O-9,12, and H-d antigens, were identified as antibody-secreting cells (ASC) with ELISPOT. Homing receptor (HR) expressions were determined. These results were compared with ASC in four patients with typhoid fever. Antibodies to S. Typhi lipopolysaccharides were assessed in cultures of ALS (antibodies in lymphocyte supernatants) and in serum with ELISA.

Results

In 49 out of 50 vaccinees, no typhoid-specific plasmablasts were seen before vaccination. On day 7, response to Vi antigen was mounted in 24/25 volunteers in the Vi, and none in the Ty21a group; response to S. Typhi and O-9,12 was mounted in 49/50 vaccinees; and to H-d in 3/50. The numbers of typhoid-specific plasmablasts (total of ASC to Vi, O-9,12 and H-d antigens) proved equal in the vaccination groups. The HR expressions indicated a mainly systemic homing in the Vi and intestinal in the Ty21a group, the latter resembling that in natural infection. Plasmablasts proved more sensitive than serum and ALS in assessing the immune response.

Conclusions

The typhoid-specific humoral responses to Vi and Ty21a vaccines are similar in magnitude, but differ in expected localization and antigen-specificity. The unforeseen O antigen-specific response in the Vi group is probably due to lipopolysaccharide contaminating the vaccine preparation. Only the response to Ty21a vaccine was found to imitate that in natural infection.

Trial Registration

Current Controlled Trials Ltd. c/o BioMed Central ISRCTN68125331 http://www.controlled-trials.com/ISRCTN68125331/     

Unsaturated vitamin B12 binding capacity and serum lysozyme activity during the marrow granulocytes reserve tests.

Unsaturated vitamin B12 binding capacity (UBBC) and serum lysozyme activity (LZM) were estimated durinng the endotoxin, prednisone and hydrocortisone marrow granulocyte reserve (MGR) pool tests. Our results showed, that no additional mechanism except the shift of MGR from marrow caused granulocytosis after typhoid vaccine administration. While the prednisone, when given orally diminished additionally the number of the physiologically destroyed neutrophils. The hydrocortisone, however, showed the results very similar to those obtained after typhoid vaccine adminstration. Thus the hydrocortisone test seems to be most useful. It gives as good information as typhoid vaccine test but does not show its side-effects.     

Treatment with a single vaginal suppository containing 15-methyl PGF2 alpha methyl ester at expected time of menstruation.

Termination of early pregnancy, by vaginal administration of prostaglandin analogues, one to three weeks after the first missed menstrual period, has advantages and disadvantages in comparison with vacuum aspiration. Some of these may be reduced if the patient is treated earlier. In the present study the effect and safety of one vaginal administration of 2.5 to 3 mg 15-methyl-PGF2 alpha methyl ester around the expected time of menstruation was evaluated in 16 women exposed to the risk of pregnancy. The overall number of treatment cycles was 35 and pregnancy was confirmed by plasma beta-HCG in eight. The treatment resulted in bleeding in all the pregnant cycles while in the nonpregnant ones it only provoked spotting and bleeding did not begin until the expected time of menstruation. Treatment with 2.5 mg 15-methyl-PGF2 alpha methyl ester resulted in complete abortion in one of three women. If the dose was increased to 3 mg all five treated women aborted. In nonpregnant patients no changes in the levels of estradiol-17 beta or progesterone at any time during the 24-hour observation period were found. Serum cortisol and prolactin but not TSH levels started to increase two hours after the start of treatment and reached a maximum after five hours. The increase coincided with the onset of uterine pain. Ovulatory cycles as judged from basal body temperature occurred in the first menstrual cycle following treatment in all nonpregnant patients. Although possible to use as a "once a month treatment" it seems preferable since the dose is the same, to postpone treatment until menstruation is delayed for a week or more.     

Genomics of immune response to typhoid and cholera vaccines

Considerable variation in antibody response (AR) was observed among recipients of an injectable typhoid vaccine and an oral cholera vaccine. We sought to find whether polymorphisms in genes of the immune system, both innate and adaptive, were associated with the observed variation in response. For both vaccines, we were able to discover and validate several polymorphisms that were significantly associated with immune response. For the typhoid vaccines, these polymorphisms were on genes that belonged to pathways of polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signalling and eventual production of antimicrobial peptides. For the cholera vaccine, the pathways included epithelial barrier integrity, intestinal homeostasis and leucocyte recruitment. Even though traditional wisdom indicates that both vaccines should act as T-cell-independent antigens, our findings reveal that the vaccines induce AR using different pathways.     

Genetic determinants of immune-response to a polysaccharide vaccine for typhoid

Differences in immunological response among vaccine recipients are determined both by their genetic differences and environmental factors. Knowledge of genetic determinants of immunological response to a vaccine can be used to design a vaccine that circumvents immunogenetic restrictions. The currently available vaccine for typhoid is a pure polysaccharide vaccine, immune response to which is T-cell independent. Little is known about whether genetic variation among vaccinees associates with variation in their antibody response to a polysaccharide vaccine. We conducted a study on 1,000 individuals resident in an area at high-risk for typhoid; vaccinated them with the typhoid vaccine, measured their antibody response to the vaccine, assayed >2,000 curated SNPs chosen from 283 genes that are known to participate in immune-response; and analyzed these data using a strategy to (a) minimize the statistical problems associated with testing of multiple hypotheses, and (b) internally cross-validate inferences, using a half-sample design, with little loss of statistical power. The first stage analysis, using the first half-sample, identified 54 SNPs in 43 genes to be significantly associated with immune response. In the second-stage, these inferences were cross-validated using the second half-sample. First-stage results of only 8 SNPs (out of 54) in 7 genes (out of 43) were cross-validated. We tested additional SNPs in these 7 genes, and found 8 more SNPs to be significantly associated. Haplotypes constructed with these SNPs in these 7 genes also showed significant association. These 7 genes are DEFB1, TLR1, IL1RL1, CTLA4, MAPK8, CD86 and IL17D. The overall picture that has emerged from this study is that (a) immune response to polysaccharide antigens is qualitatively different from that to protein antigens, and (b) polymorphisms in genes involved in polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signaling and eventual production of antimicrobial peptides are associated with antibody response to the polysaccharide vaccine for typhoid. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11568-010-9134-1) contains supplementary material, which is available to authorized users.     

Immunization against GnRH in the male camel (Camelus dromedarius): Effects on sexual behavior, testicular volume, semen characteristics and serum testosterone concentrations

The effect of immunization against gonadotrophin releasing hormone (GnRH) on sexual behavior, total scrotal size, semen characteristics and serum concentrations of testosterone, was evaluated for 24 wks in sexually mature camels (Camelus dromedarius). Eight bull camels were randomly divided into a treatment and control group. Four male camels were immunized using 2 mg GnRH - tandem-dimer conjugated to ovalbumin, (Pepscan Systems, the Netherlands) administered subcutaneously, 4 wks apart. Control male camels received the same amount of saline solution. Significant decline in serum testosterone level was observed in three immunized camels out of four, whereas one camel showed no effect. The testosterone levels reached to <1.0 ng/mL serum by week 4 after booster injection and remained suppressed through the course of the study. The total testicular volume was not affected until the end of the experiment. In treated animals, the sexual behavior negatively affected after the booster injection. Anti-GnRH vaccine had a seriously detrimental effect on the acrosin amidase activity and normal acrosome percentages in treated male camels. It is concluded that the vaccine was effective in reducing serum testosterone levels and libido, and it had a serious harmful effect on the acrosin amidase activity and percentages of spermatozoa with normal acrosome. The immunogen did not affect the total testicular volume.     

Genetically engineered Bifidobacterium animalis expressing the Salmonella flagellin gene for the mucosal immunization in a mouse model

BACKGROUND: A critical component of the host defense against enteric infections is the immunological response of the mucosal membrane, a major starting point of infectious disease, such as typhoid fever. The mucosal immune system consists of an integrated network of lymphoid tissues, mucous membrane-associated cells, and effector molecules. In the present study, we developed a recombinant Bifidobacterium animalis (B. animalis) genetically modified with the Salmonella flagellin gene for mucosal immunization as an oral typhoid vaccine. METHODS: We constructed an oral vaccine against Salmonella typhimurium, consisting of recombinant B. animalis containing the flagellin gene of Salmonella. The recombinant B. animalis was administered orally to mice every other day for 6 weeks. Anti-flagellin antibodies in the serum and stools were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: We detected significantly higher levels of flagellin-specific IgA in the serum and stools of the mice treated with the recombinant B. animalis containing the flagellin gene than was seen in those treated with parental B. animalis. CONCLUSIONS: Our findings suggest that an oral vaccination using recombinant B. animalis genetically modified with the flagellin gene of Salmonella may be effective against Salmonella infections.     

Immunotherapy of bovine ocular squamous cell carcinoma by repeated intralesional injections of live bacillus Calmette-Guérin (BCG) or BCG cell walls

Summary Thirty cows of the Dutch Friesian and the Maas-Rijn-Ijssel breed with histologically confirmed ocular squamous cell carcinoma were treated by repeated intralesional injection of live bacillus Calmette-Guérin (BCG) (n = 14) or a BCG cell-wall vaccine (n = 16). Complete regression of the primary tumour was observed in 64% and 57% of the animals respectively. In the 2-year follow-up period there was no recurrence of primary tumours. This sharply contrasts with the recurrence frequency (40%–50%) after complete remission induced by a single intralesional injection with BCG, observed in an earlier study. In 1 animal a new primary tumour developed. At necropsy metastases were present in 33% of the treated animals: in 3 of 17 animals that showed complete regression of the primary tumour and in 7 of 13 animals with partial regression or progressive disease. This did not differ significantly from results obtained after a single treatment (27%). Delayed-type hypersensitivity toM. bovis purified protein derivative (PPD) was more persistent in animals showing regression of the primary tumour than in non-responding animals. Of the animals with a positive PPD response 6 months after treatment, 79% showed tumour regression. Regression was observed in only 28% of the animals not responding to PPD after the same period of time. In conclusion: (a) recurrence of the primary tumour was not observed after repeated BCG treatment; (b) the frequency of metastases was not decreased compared to results obtained with a single treatment; (c) regression was correlated with a positive delayed-type hypersensitivity reaction to PPD (P <0.05) 6 months after treatment; (d) no significant differences were observed when the clinical results of treatment with live BCG and the BCG cell wall vaccine were compared.     

The development of lymphatic follicles in the omentum after intraperitoneal stimulation of rats

China ink and typhoid vaccine were used as peritoneal stimuli injected in single doses. The subsequent omental reaction was studied after several time intervals: 6 and 12 hours, 1, 2, 3, 4 and 8 days, 3 and 6 weeks. The omental reaction featured as lymphatic nodules connected to milky spots was compared with a primary immune response. The ultrastructure and development of the characteristic cells (lymphocytes, lymphoblasts, dendritic reticulum cells, tingible body macrophages and plasma cells) was investigated throughout the period from 6 h to 6 weeks. A special attention was devoted to ultrastructural and functional features of plasma cells.     

Operative Treatment of Typhoid Perforation of the Bowel

One hundred and twenty-one proved cases of typhoid perforation were seen in a three-year period; the incidence of perforation, 17·9%, is the highest recorded. All patients were treated by laparotomy with closure and drainage. The mortality was 29·8%, but 76% when operation was performed after the fifth day of perforation.