BACKGROUND: Vaccination against 5 prominent meningococcal serogroups (A/B/C/W/Y) is necessary for broad disease protection. We report immunopersistence through 4 years after a 2-dose (6-month interval) pentavalent MenABCWY primary vaccine series and safety and immunogenicity of a booster administered 4 years after primary vaccination. METHODS: This randomized, active-controlled, observer-blinded study was conducted in the United States and Europe. In stage 1, healthy MenACWY vaccine-naive or -experienced 10- to 25-year-olds were randomized 1:2 to receive MenABCWY and placebo or MenB-fHbp and MenACWY-CRM. Eligible participants were randomly selected to participate in stage 2, which was an open-label immunopersistence and booster extension. Immunogenicity was assessed through serum bactericidal antibody using human complement (hSBA) assays with serogroups A/C/W/Y (MenA/C/W/Y) and 4 primary serogroup B (MenB) test strains. Immunogenicity endpoints included hSBA seroprotection rates through 48 months after primary vaccination and 1 month after the booster. Safety endpoints included booster reactogenicity events and adverse events (AEs). RESULTS: Of 1379 eligible participants, 353 entered stage 2; 242 completed the 48-month blood draw after primary vaccination and 240 completed the booster vaccination phase. MenA/C/W/Y seroprotection rates remained high for 4 years following a 2-dose MenABCWY primary series (MenACWY-naive, 62.0 %-100.0 %; MenACWY-experienced, 98.7 %-100.0 %) and trended higher than those after a single MenACWY-CRM dose (MenACWY-naive, 38.1 %-95.2 %; MenACWY-experienced, 89.7 %-100.0 %). Corresponding seroprotection rates against MenB remained stable and generally higher than baseline (MenABCWY, 18.2 %-36.6 %; MenB-fHbp, 16.2 %-31.9 % across strains). Following a booster, seroprotection rates against all 5 serogroups were ≥ 93.8 % across groups. Most booster dose reactogenicity events were mild or moderate in severity, and AEs were infrequent. CONCLUSIONS: Immune responses remained high for MenA/C/W/Y and above baseline for MenB through 4 years after the MenABCWY primary series, with robust responses for all 5 serogroups observed following a booster. The MenABCWY booster had an acceptable safety and tolerability profile consistent with the primary series. NCT03135834.
- MeSH
- dítě MeSH
- dospělí MeSH
- imunogenicita vakcíny MeSH
- komplement imunologie MeSH
- lidé MeSH
- meningokokové infekce * prevence a kontrola imunologie MeSH
- meningokokové vakcíny * imunologie škodlivé účinky aplikace a dávkování MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Neisseria meningitidis imunologie MeSH
- protilátky bakteriální * krev MeSH
- sekundární imunizace * metody MeSH
- séroskupina MeSH
- vakcíny konjugované imunologie aplikace a dávkování škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Evropa MeSH
- Spojené státy americké MeSH
Wild rodents are an important source of the tick-borne pathogens Coxiella burnetii and Francisella tularensis. The aim of our study was to assess the prevalence of antibodies and possible coexistence of these pathogens in wild small mammals from three localities in the Czech Republic. A total of 614 wild small mammals (324 Apodemus flavicollis, 145 Myodes glareolus, 50 Sorex araneus, 48 A. sylvaticus, 40 A. agrarius, six Microtus arvalis and one Talpa europaea) were trapped between 2012 and 2015. Their sera or heart extracts were examined by modified indirect enzyme-linked immunosorbent assay, with the detection of antibodies against C. burnetii and F. tularensis in 12 % and 7 % of animals, respectively; coinfection was identified in 4.4 % of animals. The prevalence of C. burnetii and F. tularensis antibodies statistically differed according to animal species and sex (p < 0.05); the seroprevalence of C. burnetii (p < 0.05) also differed in the sampling period. The highest prevalence of antibodies against C. burnetii and F. tularensis was detected in the case of M. glareolus (24 % and 14 %, respectively).
- MeSH
- Arvicolinae MeSH
- Coxiella burnetii izolace a purifikace MeSH
- Francisella tularensis izolace a purifikace MeSH
- koinfekce epidemiologie mikrobiologie veterinární MeSH
- krtci MeSH
- Murinae MeSH
- nemoci hlodavců epidemiologie mikrobiologie MeSH
- prevalence MeSH
- protilátky bakteriální krev MeSH
- Q-horečka epidemiologie mikrobiologie veterinární MeSH
- rejskovití MeSH
- séroepidemiologické studie MeSH
- tularemie epidemiologie mikrobiologie veterinární MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Pertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach. METHODS: This phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27-36 weeks' gestation with crossover ≤ 72-hour-postpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were ≥ 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/neonate-related AEs of interest were recorded. RESULTS: 687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5-19.2) for anti-filamentous hemagglutinin, 20.7 (15.9-26.9) for anti-pertactin and 8.5 (7.0-10.2) for anti-pertussis toxoid. Rates of pregnancy-/neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination. CONCLUSIONS: Tdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02377349.
- MeSH
- imunita získaná od matky * MeSH
- jednoduchá slepá metoda MeSH
- lidé MeSH
- matka - expozice noxám * MeSH
- novorozenec MeSH
- pertuse * prevence a kontrola MeSH
- protilátky bakteriální krev MeSH
- těhotenství MeSH
- vakcína proti záškrtu, tetanu a černému kašli aplikace a dávkování škodlivé účinky MeSH
- vakcinace MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze IV MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Pertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization. METHODS: This phase IV, multi-country, open-label study assessed the immunogenicity and safety of infant primary vaccination with DTaP-HepB-IPV/Hib and 13-valent pneumococcal conjugate vaccine (PCV13). Enrolled infants (6-14 weeks old) were born to mothers who were randomized to receive reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) during pregnancy (270/7-366/7 weeks' gestation) with crossover immunization postpartum. All infants received 2 or 3 DTaP-HepB-IPV/Hib and PCV13 doses according to national schedules. Immunogenicity was assessed in infants pre- and 1 month post-primary vaccination. The primary objective was to assess seroprotection/vaccine response rates for DTaP-HepB-IPV/Hib antigens 1 month post-primary vaccination. RESULTS: 601 infants (Tdap group: 296; control group: 305) were vaccinated. One month post-priming, seroprotection rates were 100% (diphtheria; tetanus), ≥98.5% (hepatitis B), ≥95.9% (polio) and ≥94.5% (Hib) in both groups. Vaccine response rates for pertussis antigens were significantly lower in infants whose mothers received pregnancy Tdap (37.5-77.1%) versus placebo (90.0-99.2%). Solicited and unsolicited adverse event rates were similar between groups. Serious adverse events occurred in 2.4% (Tdap group) and 5.6% (control group) of infants, none were vaccination-related. CONCLUSIONS: Pertussis antibodies transferred during pregnancy may decrease the risk of pertussis infection in the first months of life but interfere with the infant's ability to produce pertussis antibodies, the clinical significance of which remains unknown. Safety and reactogenicity results were consistent with previous experience. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02422264.
- MeSH
- hemofilové vakcíny imunologie MeSH
- kojenec MeSH
- kombinované vakcíny imunologie MeSH
- lidé MeSH
- následné studie MeSH
- pneumokokové vakcíny imunologie MeSH
- poliovirová vakcína inaktivovaná imunologie MeSH
- protilátky bakteriální krev MeSH
- těhotenství MeSH
- vakcína proti diftérii, tetanu a pertusi imunologie MeSH
- vakcína proti hepatitidě B imunologie MeSH
- vakcína proti záškrtu, tetanu a černému kašli aplikace a dávkování MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze IV MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Definition of Pseudomonas aeruginosa (Pa) microbiological status is essential for patients' inclusion in clinical trials. The aim of this study was to agree on the definitions of Pa infection status for initial infection, eradication and chronic infection to be used in clinical trials and to propose additional future study areas. METHODS: An exhaustive literature search was performed. The clinimetric properties of different definitions of Pa microbiological status were evaluated. RESULTS: Historical studies have mostly used culture-based definitions, although some have also involved complementary anti-Pa antibodies. Clinimetric analysis showed great variability in the definitions used, leading to differences in reliability, validity, responsiveness to treatment and correlation with outcome measures. Use of serology for initial Pa infection and successful Pa eradication introduced a greater level of complexity as antibody tests are not standardised. Moreover, the chronology of the immune response to Pa antigenic determinants was not completely clear. Chronic Pa infection was characterized by high levels of antibodies and good concordance between culture results and serology. CONCLUSIONS: Microbiological monitoring, regular sampling from the airways and standardization of culture methods remain essential requisites for microbiological definitions. Despite limitations, serology should be incorporated in the definitions of initial infection and eradication used in clinical trials to better classify patients at enrolment, mainly in non-expectorating children. This requires standardization of serological testing.
- MeSH
- cystická fibróza * diagnóza mikrobiologie MeSH
- lidé MeSH
- protilátky bakteriální krev MeSH
- pseudomonádové infekce * diagnóza etiologie imunologie MeSH
- Pseudomonas aeruginosa * imunologie izolace a purifikace MeSH
- sérologické testy metody normy MeSH
- terminologie jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Rickettsialpox is a febrile illness caused by the mite-borne pathogen Rickettsia akari. Several cases of this disease are reported worldwide annually. Nevertheless, the relationship between the immunogenicity of R. akari and disease development is still poorly understood. Thus, misdiagnosis is frequent. Our study is aiming to identify immunogenic proteins that may improve disease recognition and enhance subsequent treatment. To achieve this goal, two proteomics methodologies were applied, followed by immunoblot confirmation. RESULTS: Three hundred and sixteen unique proteins were identified in the whole-cell extract of R. akari. The most represented protein groups were found to be those involved in translation, post-translational modifications, energy production, and cell wall development. A significant number of proteins belonged to amino acid transport and intracellular trafficking. Also, some proteins affecting the virulence were detected. In silico analysis of membrane enriched proteins revealed 25 putative outer membrane proteins containing beta-barrel structure and 11 proteins having a secretion signal peptide sequence. Using rabbit and human sera, various immunoreactive proteins were identified from which the 44 kDa uncharacterized protein (A8GP63) has demonstrated a unique detection capability. It positively distinguished the sera of patients with Rickettsialpox from other rickettsiae positive human sera. CONCLUSION: Our proteomic analysis certainly contributed to the lack of knowledge of R. akari pathogenesis. The result obtained may also serve as a guideline for a more accurate diagnosis of rickettsial diseases. The identified 44 kDa uncharacterized protein can be certainly used as a unique marker of rickettsialpox or as a target molecule for the development of more effective treatment.
- MeSH
- chromatografie kapalinová MeSH
- králíci MeSH
- lidé MeSH
- molekulární modely MeSH
- molekulová hmotnost MeSH
- proteiny vnější bakteriální membrány chemie imunologie metabolismus MeSH
- proteomika metody MeSH
- protilátky bakteriální krev MeSH
- Rickettsia akari imunologie izolace a purifikace metabolismus MeSH
- sekundární struktura proteinů MeSH
- skvrnité horečky diagnóza imunologie MeSH
- tandemová hmotnostní spektrometrie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: The aim of this study is to evaluate the seroprevalence of antibodies of Borrelia burgdorferi sensu lato (Bbsl) and Leptospira interrogans sensu lato (Lisl) and their possible concurrence in domestic cats living in variable conditions in South Moravia in the district of Brno and its environs. Additional objectives were to discover possible differences in seroprevalence between groups of cats living in different living conditions, and to determine the spectrum of Leptospira serogroups in cats in the same places. MATERIAL AND METHODS: A total of 360 blood sera from domestic cats of 3 different sets were collected during the period 2013-2015. All samples were examined using ELISA for the detection of IgM and IgG antibodies against Bbsl, and the microscopic agglutination test (MAT) for the detection of antibodies against 8 serogroups of Lisl. RESULTS: The ELISA method determined 15.8%, 4.8% and 10.3% IgM anti-Borrelia antibodies in the patient group, shelter cats and street cats, respectively. IgG anti-Borrelia antibodies were found in 6.2%, 9.5%, 5.2%, respectively. Antibodies specific for 5 Leptospira serogroups were detected by the use of MAT in 8.8%, 9.5% and 10.3% of cats from the investigated groups. The total positivity of all examined cats for anti-Borrelia antibodies was 18.0% and for anti-Leptospira - 9.2%. CONCLUSIONS: Cats can be infected with both Bbsl and Lisl. The obtained results are exclusive to the city of Brno and its environs, and are comparable to the limited previous studies. There is a need for further studies of clinical signs of both infections and the possible transmission of Leptospira by ticks.
- MeSH
- Borrelia burgdorferi komplex izolace a purifikace MeSH
- kočky MeSH
- Leptospira interrogans izolace a purifikace MeSH
- leptospiróza epidemiologie mikrobiologie veterinární MeSH
- lymeská nemoc epidemiologie mikrobiologie veterinární MeSH
- nemoci koček epidemiologie mikrobiologie MeSH
- prevalence MeSH
- protilátky bakteriální krev MeSH
- séroepidemiologické studie MeSH
- zvířata MeSH
- Check Tag
- kočky MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
In Lyme disease, the interpretation of diagnostic assays is often misunderstood. Cross-reactions of Borrelia proteins with antigens from other bacterial species are well known. Therefore, to diagnose Lyme disease, the finding of positive IgM antibodies must be accompanied by objectively verified clinical signs and a history of a possible tick exposure. Positive Borrelia IgM antibodies in healthy individuals with nonspecific clinical symptoms are likely a false-positive result for Lyme disease and neither long-term antibiotic treatment nor cycling of different antibiotic regimens is beneficial. To date, there is clear evidence that positive serology does not indicate infection with Borrelia species. Borrelia serology has been reported to be positive for months or years in ∼20% of healthy patients who had experienced Lyme disease in the past. Thus, serology as a single diagnostic tool has a very limited value and should be used only to support clinically suspected cases.
- MeSH
- Borrelia imunologie MeSH
- imunoglobulin G krev MeSH
- imunoglobulin M krev MeSH
- kousnutí klíštětem MeSH
- lidé MeSH
- lymeská nemoc diagnóza imunologie MeSH
- protilátky bakteriální krev MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Rickettsia rickettsii is the causative agent of Brazilian spotted fever (BSF), for which humans and dogs are both susceptible. Dogs are sentinels in serological surveys, however, canine disease is rarely reported. Therefore, we aimed to evaluate natural infection by spotted fever group (SFG) Rickettsia spp. in dogs and ticks collected from domiciles close to forest fragments, featuring domestic-wildlife interface areas. Samples from 115 dogs and 135 ixodids were assessed by polymerase chain reactions (PCR) targeting the gltA gene for Rickettsia spp. and the ompA gene for the SFG rickettsial species. One dog (0.87%; 1/115) was positive for R. rickettsii. This dog presented nonspecific laboratory and clinical abnormalities (thrombocytopenia, hyperproteinemia, lymph node enlargement, emaciation, anorexia, and lethargy). Rickettsia parkeri was identified in 2.96% (4/135) of the ticks (Amblyomma sculptum, A. aureolatum, and Rhipicephalus sanguineus). This study confirmed the presence of SFG bacteria in non-endemic and preserved locations, where domestic and wild populations interact. We reinforce the fact that the dog is susceptible to natural R. rickettsii infection. Although this is a rare finding, preventive measures should be taken against BSF in the studied areas. Finally, R. parkeri infection is possibly being demonstrated in A. sculptum for the first time.
- MeSH
- klíšťata mikrobiologie MeSH
- nemoci psů diagnóza mikrobiologie MeSH
- polymerázová řetězová reakce MeSH
- protilátky bakteriální krev MeSH
- psi MeSH
- Rickettsia klasifikace genetika izolace a purifikace MeSH
- skvrnité horečky diagnóza mikrobiologie veterinární MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Brazílie MeSH
Tularemia caused by Francisella tularensis is a zoonotic infection of the Northern Hemisphere that mainly affects the skin, lymph nodes, bloodstream, and lungs. Other manifestations of tularemia are very rare, especially those with musculoskeletal involvement. Presenting in 2016, we diagnosed two cases of periprosthetic knee joint infections (PJI) caused by Francisella tularensis in Europe (one in Switzerland and one in the Czech Republic). We found only two other PJI cases in the literature, another knee PJI diagnosed 1999 in Ontario, Canada, and one hip PJI in Illinois, USA, in 2017. Diagnosis was made in all cases by positive microbiological cultures after 3, 4, 7, and 12 days. All were successfully treated, two cases by exchange of the prosthesis, one with debridement and retention, and one with repeated aspiration of the synovial fluid only. Antibiotic treatment was given between 3 weeks and 12 months with either ciprofloxacin-rifampin or with doxycycline alone or doxycycline in combination with gentamicin. Zoonotic infections should be considered in periprosthetic infections in particular in culture-negative PJIs with a positive histology or highly elevated leukocyte levels in synovial aspiration. Here, we recommend prolonging cultivation time up to 14 days, performing specific PCR tests, and/or conducting epidemiologically appropriate serological tests for zoonotic infections, including that for F. tularensis.
- MeSH
- antibakteriální látky terapeutické užití MeSH
- bakteriologické techniky MeSH
- Francisella tularensis MeSH
- infekce spojené s protézou diagnóza farmakoterapie mikrobiologie MeSH
- kolenní kloub účinky léků mikrobiologie MeSH
- lidé MeSH
- protilátky bakteriální krev MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- synoviální tekutina mikrobiologie MeSH
- tularemie komplikace diagnóza farmakoterapie MeSH
- výsledek terapie MeSH
- zoonózy diagnóza farmakoterapie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- přehledy MeSH