Characteristics of the mechanisms of the immune response in typhoid fever and the bacterial carrier state

During the acute period of typhoid fever, as well as in the early and, partially, late convalescence periods, a considerable increase in the level of T-lymphocytes and their helper activity and, in some cases, in the number of B- and D-cells and the populations of neutrophils with receptors for C3 and Fc IgG was observed. In chronic carriers immune shifts of a different character have been recorded: an increase in suppressor activity and a decrease in the number of the above-mentioned neutrophils. These data prompt the use of immunological criteria for the prediction of chronic carrier state in typhoid fever.     

Specific antibodies bound to secretory IgA in the sera of patients with intestinal infections]

Specific IgA and sIgA antibodies were studied in the sera of patients suffering from various intestinal diseases (dysentery, salmonellosis, typhoid fever, chronic typhoid carrier state) and in the sera of healthy persons immunized by parenteral route with typhoid alcohol vaccine. The nature of antibodies was identified in Coombs' test, using monospecific antisera to alpha-chain and to the secretory component. IgA and sIgA antibodies were revealed most frequently in the sera of dysentery patients and of chronic typhoid carriers. No sIgA antibodies were found in the sera of subcutaneously immunized persons. The presence of specific sIgA antibodies in the serum reflects the participation of local immune mechanisms in the formation of systemic immunity in the intestinal infections.     

Epidemiology of typhoid carriers among blood donors and patients with biliary, gastrointestinal and other related diseases

Enteric fever due to Salmonella Typhi is a major public health problem. Typhoid carriers have high titres of Vi agglutinins in their sera. We worked out the baseline data for Vi agglutinins from 705 healthy blood donors (controls) by ELISA and compared it with 446 patients with biliary, gastrointestinal and other related diseases (cases). The samples were divided into five groups based on the disease condition of the patients from whom they were collected. Group A (n=196) consisted of patients with stones in the gall bladder/common bile duct and Group B (n=27) with gall bladder carcinoma. Group C (n=33) comprised patients with carcinoma of the pancreas/ampulla, obstructive jaundice and/or cholangiocarcinoma. Group D (n=112) had patients with acute/chronic pancreatitis, abdominal pain, intestinal obstruction, peritonitis, carcinoma oesophagus, chronic diarrhoea, gastrointestinal bleeding and dyspepsia. Group E (n=78) included patients with miscellaneous diseases. The mean absorbance value obtained for healthy subjects +3 standard deviations was taken as the cut-off value for a positive typhoid carrier. In Group A, 10.2% samples were positive; in Group B, 7.4%; in Group C, 12.0%; in Group D, 9.8% and in Group E, 9.0%. There was a highly significant (P <0.001) increase in the presence of Vi agglutinins in the cases compared to the controls. High prevalence of typhoid carriers occurs in patients with biliary, gastrointestinal and other related diseases. Vi serology employing highly purified Vi antigen offers a practical and cost-effective way of screening for S. Typhi carriers.     

Leukocyte migration inhibition by a specific antigen in human typhoid fever.

Cellular reactivity to heat-killed Salmonella typhi antigen was investigated by the leukocyte migration inhibition (LMI) method in 33 S. typhi infected patients and in 32 control persons. In the typhoid group a statistically significant LMI was observed as compared to the members of the control group. A correlation was found between the level of the cellular sensitivity and the time elapsed between onset of the disease and performance of the test. Previous typhoid vaccination had no influence on the LMI. No correlation was found between the agglutinin titres and the sensitivity demonstrated by the LMI test. The value of the method in studies of cellular immunity in typhoid fever is discussed.     

Epidemiological and laboratory criteria in the assessment of meningococcus carrier state]

A study was made of the duration of meningococcus carrier state, immunological indices and group-specific properties of meningococci isolated from them. The periods of meningococcus discharge were studied in 738 persons. Three categories of the carrier state were revealed: a single discharge (67% of the carriers), of average duration (up to 4 weeks), and prolonged. Greater indices of group-specific antibodies (in the passive hemagglutination test) were revealed in the carriers with prolonged presence of meningococci in the nasopharynx. Dynamics of immunological indices and periods of the carrier state formation in the foci of infection permitted to characterize the prolonged carrier state as a latent form of meningococcus infection. A study of the group-specific properties in 1845 strains and comparison of the group-specific pattern of the circulating strains with the epidemic situation indicated that meningococci of group A were not only epidemic, but also more virulent.     

The neutrophil receptor apparatus in typhoid fever

In 157 typhoid fever patients and 36 practically healthy persons the content of neutrophils forming complement-dependent rosettes (NEAC rosette-forming cells), as well as rosettes with sheep red blood cells (NE rosette-forming cells) and with typhoid erythrocyte diagnosticum (NS rosette-forming cells), has been studied. The data obtained in this investigation indicate that antigen-binding neutrophils play an active functional role in the pathogenesis of typhoid fever at its acute stage. The values characterizing the content of N rosette-forming cells may be used as a criterion for the evaluation of the severity of infection, as well as for the prognostication of complications and relapses.     

Effect of the ABO blood group phenotype on the Staphylococcus aureus bacterial carrier state

326 employees of 4 medical institutions (1 regional hospital, 2 city hospitals and a maternity clinic) were examined for the presence of S. aureus carriership. Examinations were made every 3 months for 3 recent years. The results of these examinations were compared with the distribution of the blood groups in the AB0 system among the carriers. Constant and malignant carrier state was detected mainly in persons with blood group A.     

A comprehensive evaluation of the biological properties of the causative agents of typhoid fever isolated from patients and carriers

The biological properties of 106 S. typhi cultures were studied; of these, 59 cultures were isolated from 45 chronic carriers and 47 cultures, from 23 typhoid fever patients. According to the degree of their virulence (CPD50 in the continuous cell-line culture Hep-2), the strains isolated from the patients were more virulent than those isolated from the chronic carriers. The mean value of lg CPD50 was 5.76 +/- 0.04 for the patients and 6.86 +/- 0.03 for the chronic carriers. The strains isolated from the patients showed greater variability in the degree of their virulence. The study of the plasmid spectrum showed that 9.4 +/- 5.6% of the strains contained plasmids. From the patients plasmid-containing strains were isolated more frequently than from the carriers (14.9 +/- 2.5% and 5.1 +/- 2.9%). Multiresistance to antibiotics in combination with the presence of plasmids was detected in 6 strains isolated from the typhoid patients with morbidity having the character of outbreaks.     

Prevention of the chronic persistence of typhoid microbes in rabbits with thymostimulin

Typhoid infection was reproduced by introducing the infective agent into the bone marrow of noninbred rabbits. After the injection of thymostimulin on the first day of infection the release of typhoid bacilli continued for 1-3 weeks; when thymostimulin was injected on day 20, the release of typhoid bacilli stopped in two weeks. In the control group the release of typhoid bacilli continued during the whole term of observation. The injection of thymostimulin at an early period after infection was thus found to prevent the development of chronic typhoid infection with the elimination of the infective agent from the body of rabbits.     

Antityphoid and antitetanic intradermal vaccination of chronic neuropsychic patients in a typhoid fever outbreak.

Intradermal immunization of 229 chronic neuropsychic patients in Gura Ocnitzei Sanatorium, D?mbovitza County, where a typhoid fever outbreak burst, was performed with a freeze-dried typhoid vaccine, suspended in purified and concentrated tetanic anatoxin. Adverse reactions were minimal and immunologic response, evaluated by laboratory tests, was good, reaching the level of that obtained as a result of classic vaccination methods (subcutaneous antityphoid and intramuscular anti-tetanic). Both after vaccination and also booster O and H agglutinating titers increased 4-7 times and anti-S. typhi. seroprotecting effect reached and maintained a high level. Moreover, antityphoid vaccination permitted epidemic focus limiting and its complete extinguishing after booster. Antitetanic vaccination resulted in protecting titers settlement (greater than or equal to 0.01 IU/ml) in all previously non-protected persons (1/3 of all subjects) and in the increase of protecting titers, existing before vaccination in the other persons.     

The pharyngeal beta-hemolytic streptococcal carrier state among blood donors

459 blood donors aged 18-50 years were examined in 1987-1988 in Moscow. Among them, carrier state with respect to beta-hemolytic streptococci was detected in 107 donors (23.3%). The number of carriers gradually decreased with the increase of age of the examined donors. Group C streptococci occurred least of all (6.9%). Group A beta-hemolytic streptococci were isolated in 16.7% of the carriers. The isolation rate of streptococci from blood achieved its maximum in autumn and winter months and did not depend on preceding diseases, unhealthy working conditions, the rhesus factor and, with the exception of group A streptococci, the blood group. Among tonsillectomized donors carrier state with respect to beta-hemolytic streptococci occurred 2.2 times less frequently than among donors who had not undergone tonsillectomy. Carrier state with respect to beta-hemolytic streptococci was accompanied by higher levels of salivary sIgA antibodies to polysaccharide A, serum antibodies to polysaccharide A and circulating polysaccharide A. All beta-hemolytic streptococci were sensitive to erythromycin. All groups of streptococci showed the highest percentage of cultures resistant to gentamicin and tetracycline. In 100% of cases group A streptococci were sensitive to benzylpenicillin, methicillin, ampicillin, erythromycin and lincomycin.     

Significance of persons with different blood groups in the influenza type A epidemic process

To study the susceptibility of persons with different blood groups to influenza A, the presence of infection in a group of young children placed under constant observation for 6 years (1974-1980) and in a group of donors observed during 1979-1980 was studied in different epidemic situations. The susceptibility of the persons under observation to type A influenza viruses was shown to depend both on the blood group of the subjects and on the properties of circulating viruses. Persons with group B (III) blood were more susceptible to the virus at the period when new antigenic variants and serotypes appeared, persons with group O (I) blood were more susceptible to influenza infection at the period of the circulation of virulent strains, while persons with group A (II) blood were more susceptible at the period when less virulent strains circulated. The susceptibility of persons with different blood groups was found to change as changes in the properties of the strains occurred in the process of their circulation.     

Dynamics of the types of carrier state and their relationship to the phage group characteristics of pathogenic staphylococci]

A total of 305 persons belonging to the medical staff of a hospital surgery unit were subjected to multiple examinations during period of up to 8 years. 2,354 staphylococcal strains isolated from these subjects were studied, and the following types of carrier state were determined: constant (23.6 +/- 2.43%), intermittent (57.4 +/- 2.83%), resident (7.9 +/- 1.54%), and the stable absence of carrier state (11.1 +/- 1.60%). An increase in the number of examinations and the terms of observation resulted in a regular increase in the number of intermittent carriers at the expense of constant carriers and persons not identified as carriers. Against this background resident carriers constituted a relatively more stable group. Carrier states of the resident type were connected with staphyloccci belonging to various phage groups without pronounced differences in the frequency with which any of the phage groups occurred.     

Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and typhoid susceptibility in Asian Malay population in Malaysia

Typhoid fever is a major health problem with frequent outbreaks in Kelantan, Malaysia. Prevalence of TLR4 gene polymorphisms varies with ethnic groups (0-20%) and predisposean individual to gram-negative infections. The prevalence rate of TLR4 Asp299Gly and Thr399lle polymorphisms in the Malay population or the influence of these on typhoid fever susceptibility is not yet reported. 250 normal and 304 susceptible Malay individuals were investigated for these polymorphisms using allele-specific PCR and analysed for its association with typhoid fever susceptibility. The total prevalence of polymorphisms in the normal population was 4.8% in comparison to 12.5% in the susceptible population (p?=?0.002). An increased frequency of both polymorphisms was observed in the susceptible population (p?相似文献   

The detection of antigenemia in typhoid patients at different periods in the course of the infection

The enzyme immunoassay of serum samples, obtained from 37 typhoid patients and previously subjected to bacteriological study with negative results, permitted the detection of S. typhi specific antigens and, as a consequence, the rapid diagnosis of the disease. The prevalence of various antigenic components of S. typhi was observed at different stages of infection. The presence of surface O and Vi antigens was characteristic of acute stages of S. typhi infection. At the same time L-form antigens, in rare cases in combination with surface O and Vi antigens, were characteristic of patients at the period following the acute stage of the disease, as well as chronic carriers. This is indicative of the necessity of introducing specific antibodies to the antigenic determinants of S. typhi L forms into the assortment of diagnostic immune preparations.     

Facility-based disease surveillance and Bayesian hierarchical modeling to estimate endemic typhoid fever incidence,Kilimanjaro Region,Tanzania, 2007–2018

Growing evidence suggests considerable variation in endemic typhoid fever incidence at some locations over time, yet few settings have multi-year incidence estimates to inform typhoid control measures. We sought to describe a decade of typhoid fever incidence in the Kilimanjaro Region of Tanzania. Cases of blood culture confirmed typhoid were identified among febrile patients at two sentinel hospitals during three study periods: 2007–08, 2011–14, and 2016–18. To account for under-ascertainment at sentinel facilities, we derived adjustment multipliers from healthcare utilization surveys done in the hospital catchment area. Incidence estimates and credible intervals (CrI) were derived using a Bayesian hierarchical incidence model that incorporated uncertainty of our observed typhoid fever prevalence, of healthcare seeking adjustment multipliers, and of blood culture diagnostic sensitivity. Among 3,556 total participants, 50 typhoid fever cases were identified. Of typhoid cases, 26 (52%) were male and the median (range) age was 22 (<1–60) years; 4 (8%) were aged <5 years and 10 (20%) were aged 5 to 14 years. Annual typhoid fever incidence was estimated as 61.5 (95% CrI 14.9–181.9), 6.5 (95% CrI 1.4–20.4), and 4.0 (95% CrI 0.6–13.9) per 100,000 persons in 2007–08, 2011–14, and 2016–18, respectively. There were no deaths among typhoid cases. We estimated moderate typhoid incidence (≥10 per 100 000) in 2007–08 and low (<10 per 100 000) incidence during later surveillance periods, but with overlapping credible intervals across study periods. Although consistent with falling typhoid incidence, we interpret this as showing substantial variation over the study periods. Given potential variation, multi-year surveillance may be warranted in locations making decisions about typhoid conjugate vaccine introduction and other control measures.     

Humoral imunity to pertussis in children with diabetes of type 1

To determine the state of humoral immunity to pertussis in children with insulin-dependent diabetes, IgG antibodies to pertussis toxin (PT) were determined in blood serum samples by means of EIA. In a group of children aged up to 6 years the highest percentage (100%) received the complete course of vaccination against pertussis with Russian adsorbed DPT vaccine, containing whole-cell pertussis monovaccine, while in a group over 6 years the complete vaccination course (3 vaccinations and 1 revaccination) had 53.4% of children. Pertussis morbidity was considerably higher in nonvaccinated subjects than in children with 4-fold vaccination (p < 0.001). The coefficient of association (Q) was 0.84. Children of all age groups were found to have low and average titers of antibodies to PT. The regressive analysis showed a decrease in antibodies in persons completely immunized against pertussis by the age of 6 years old. The presence of antibodies in nonimmunized persons showed that cases of pertussis or carrier state took place among the population. High titers of antibodies, indicative of recent cases of pertussis, were registered in all age groups, but high titers of antibodies were registered mostly in the group of children over 13 years old (p < 0.05), which confirmed an increase in pertussis morbidity in adolescents. Thus, vaccination against pertussis effectively protected children with diabetes of type 1, aged up to 6 years. For more prolonged protection the vaccination and revaccination of children aged over 4 years old is necessary.     

Fibrinolysis in diabetes mellitus

In 198 diabetic patients of type I and type II and in 111 healthy persons of a control group the activity of fibrinolysis was investigated before and after a venous occlusion test of ten minutes. Spontaneous fibrinolysis was significantly diminished in diabetics of both types in comparison to the control group. A relationship to the degree of seriousness of retinopathy could not be identified in type I. The activity of fibrinolysis decreased in all test persons in old age. In diabetics patients of type II as well as in that age group being more than 56 years old there were smaller activities of fibrinolysis at higher stages of retinopathy. A negative linear correlation of this spontaneous activity of fibrinolysis could be found for the duration of the disease as well as for age. Different forms of diabetic therapy and the sex allowed no influence of the activity of fibrinolysis to be recognized. An increase of the activity of fibrinolysis after congestion could be established in diabetics as well as in the control group. After venous congestion the fibrinolytic activity showed no differences any longer in diabetics and in the control group, with age, duration of the disease and form of therapy being taken into consideration. Before and after venous congestion a negative linear correlation could be revealed between the activity of fibrinolysis and the height of blood sugar level. Therefore, the real blood sugar concentration should be taken into account in evaluating the fibrinolytic activity.     

An immunoblotting as a method for the diagnosis of typhoid fever

The patients' sera had been referred to the National Salmonella Centre for routine Widal serology. Sera were predominately from patients suspected of having been infected with Salmonella Typhi, but also included one serum from patient with typhoid fever who was culture positive for Salmonella Typhi. The immunoblotting procedure using Salmonella Typhi somatic (O=9,12 LPS) and flagellar (H=d) antigens was used for preliminary testing of selected patients sera previously evaluated by Widal agglutination assay as containing different levels of antibodies against O and/or H antigens of Salmonella Typhi. Following Chart et al., immunoblotting reactions were graded between 0 and 3, with 0 indicating an absence of antibody binding, and 3 where antibody binding was readily observed. Sera giving reaction of 2 or 3 were considered to be antibody positive for this study. Positive immunoblotting reaction to O=9,12 LPS antigen was obtained only with the serum of patient with typhoid fever. Presence of specific anti-LPS antibodies was also observed in two other patients' sera diluted 1:50, and in case of one of them also in dilution 1:200, but intensity of antigen-antibody reaction was under positive result criterion. The most other sera positive to O=9,12 antigen in law dilutions (1:50, 1:100) by Widal assay, showed the traces of non-specific reaction by immunoblotting. Presence of positive antigen-antibody reaction was indicated for five sera in dilution 1:50 when tested with the >55 kDa H=d flagellar protein subunit, including the serum of patient with typhoid fever. Only in this serum the high level of specific antibodies was detected also in dilution 1:200, what was not observed in case of the other four, which appeared negative. All the other sera were shown not to contain antibodies to flagella antigen. Although the presented results are preliminary and additional study of more sera of people infected with Salmonella Typhi is needed, it can be concluded after Chart et al., that an immunoblotting procedure incorporating O=9,12 LPS and flagellar H=d antigens is a useful method for providing serological evidence of infection with Salmonella Typhi. In our opinion it can serve as a rapid test for the diagnosis of typhoid fever.     

Reactivity of typhoid patients sera with stress induced 55 kDa phenotype in Salmonella enterica serovar Typhi

Salmonella faces a variety of stresses including acid and heat, in the natural environment whether in the gastrointestinal tract of mammalian host or in the external environment during transmission where survival and multiplication is a priority for the pathogen. In the present study, Salmonella enterica serovar Typhi was grown under acid (inorganic and organic) as well as heat stress and the outermembrane protein (OMP) profiles were compared. A 55 kDa OMP was found to be expressed with high intensity under the selected stress conditions in comparison to normal conditions. The protein expressed under acidic stress reacted with antibodies raised against heat shock protein indicating the similarity of atleast some of the epitopes. In vivo immunogenicity (reactivity with typhoid patient sera) revealed that the 55kDa protein under each stress condition was reactive with 83% of the typhoid sera. In the light of role of the stress induced proteins in pathogenesis of microbial infections and their immunogenic potential, these findings may be relevant for a better understanding of the host-microbe interactions and for future development of diagnostic and preventive strategies.