RESUMO
After the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), serotype replacement has occurred in Japan, and serotype 24 has become the most common serotype in paediatric invasive pneumococcal disease (IPD). To understand the characteristics of serotype 24-IPD in Japanese children in the post-PCV13 era, we conducted a retrospective study in children aged ≤15 years from 2010 to 2020 using a database of paediatric IPD surveillance in Chiba prefecture, Japan. We identified a total of 357 IPD cases and collected clinical information on 225 cases (24: 32 cases, non-24: 193 cases). Compared with the non-serotype 24-IPD, serotype 24-IPD was independently related to be <2 years of age [odds ratio (OR) 3.91, 95% confidence interval (CI) 1.47-10.44; P = 0.0064] and bacteremia (OR 2.28, 95% CI 1.01-5.13; P = 0.0475), as a result of the multivariate regression analysis. We also conducted a bacterial analysis, and the isolates of serotype 24-IPD had tendencies of PCG-susceptible (24: 100.0%, non-24: 61.3%; P < 0.0001) and macrolide-resistance (24: 100.0%, non-24: 87.3%; P = 0.0490). Their multilocus sequence typing was mostly ST2572 and the variants, which were unique to Japan. This tendency might have been a result of the progress made in the Japanese PCV13 immunisation programme.
Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Criança , Pré-Escolar , Humanos , Incidência , Lactente , Japão/epidemiologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas , Estudos Retrospectivos , SorogrupoRESUMO
This is the first report on a population-based prospective study of invasive group B streptococcus (GBS) disease among children aged <15 years conducted over a period of 11 years in Japan. This study investigated the incidence and clinical manifestations of invasive GBS disease in children in Chiba Prefecture, Japan, and analysed the serotypes and drug susceptibility of GBS strains isolated during the study period. Overall, 127 episodes of invasive GBS disease were reported in 123 patients. Of these, 124 were observed in 120 patients aged <1 year, and the remaining three episodes were reported in a 9-year-old child and two 14-year-old children with underlying disease. For patients aged <1 year, the incidence rate per 1000 live births was 0.24 (0.15-0.36). The incidences of early-onset disease and late-onset disease were 0.04 (0.0-0.09) and 0.17 (0.08-0.25), respectively. The rate of meningitis was 45.2%, and the incidence of GBS meningitis was higher than that of other invasive diseases among children in Japan. Of the 109 patients for whom prognosis was available, 7 (6.4%) died and 21 (19.3%) had sequelae. In total, 68 strains were analysed. The most common were serotype III strains (n = 42, 61.8%), especially serotype III/ST17 strains (n = 22, 32.4%). This study showed that the incidence of invasive GBS disease among Japanese children was constant during the study period. Because of the high incidence of meningitis and disease burden, new preventive strategies, such as GBS vaccine, are essential.
Assuntos
Infecções Estreptocócicas , Streptococcus agalactiae , Humanos , Criança , Japão/epidemiologia , Estudos Prospectivos , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , SorogrupoRESUMO
We describe a patient with invasive Haemophilus influenzae type b (Hib) infection despite being completely immunized by a conjugate Hib vaccine. Although Hib vaccination has contributed to significant reduction in invasive Hib infection, there are some case reports of invasive Hib infections despite immunization. Immunoglobulin (Ig) deficiency is the main cause of primary vaccine failure, and IgG2 subclass deficiency is known to be the leading cause. A previously healthy 13-month-old boy visited the outpatient clinic with a 5-day history of fever (40.0 °C), cough, and vomiting, and was diagnosed with bacterial meningitis, purulent pericarditis, and arthritis. Hib was recovered from blood, cerebrospinal fluid, and pericardial fluid. Immunological examination revealed subnormal IgG and IgA titers at 13 and 17 months of age. Serum IgG2 titer was recovered at 17 months of age despite being low at 13 months. Comprehensive gene analysis for primary immunodeficiency syndromes (primary antibody deficiency, common variable immunodeficiency, and toll-like receptor abnormalities) were negative. The antibody titer against Hib [anti-polyribosylribitol phosphate (PRP) antibody] was lower than the long-term protective titer (1.0 µg/ml) at 13 months of age, but was reactively increased to 2.38 µg/mL two months after booster immunization. Transient hypogammaglobulinemia of infancy (THI) is described as an accentuation and prolongation of the physiologic Ig nadir that is normally observed during infancy and defined as low IgG and IgA levels in the first three years of life. We speculate that he developed an invasive Hib infection as a result of primary Hib vaccine failure caused by THI.
Assuntos
Agamaglobulinemia , Infecções por Haemophilus , Vacinas Anti-Haemophilus , Haemophilus influenzae tipo b , Anticorpos Antibacterianos , Infecções por Haemophilus/tratamento farmacológico , Humanos , Lactente , Masculino , Vacinas ConjugadasRESUMO
Lenalidomide maintenance therapy prolonged progression-free survival (PFS) versus placebo in elderly patients with diffuse large B-cell lymphoma (DLBCL) responding to induction chemotherapy in the phase 3 REMARC study. This subpopulation analysis assessed the impact of lenalidomide maintenance and treatment-emergent adverse events (TEAEs) on health-related quality of life (HRQOL). Global health status (GHS), and physical functioning and fatigue subscales were evaluated in patients who completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire-C30 v3.0. The impact of TEAEs classified post hoc as subjective (patients can feel) or observable (only measurable by physicians) on dose reductions and discontinuations was assessed. Among 457 patients (lenalidomide, n = 229; placebo, n = 228), mean (standard deviation) GHS was similar between treatment arms [68·2 (20·7) Versus 72·0 (17·8)] at randomisation and remained similar during maintenance. Patients receiving lenalidomide experienced no meaningful changes in GHS, physical functioning, or fatigue. Observable TEAEs were more common (81·1% Versus 66·3%) and more likely to lead to dose reductions, than subjective TEAEs in both arms. PFS was superior in the lenalidomide arm regardless of dose reduction. Lenalidomide maintenance prolonged PFS and did not negatively impact HRQOL in patients with DLBCL despite TEAEs being more common, when compared with placebo.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Lenalidomida/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Quimioterapia de Manutenção , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Lenalidomida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
Individuals with immunosuppressive condition have a high risk of invasive Haemophilus influenzae type b (Hib) infection. In Japan, routine Hib vaccination program for children under 5 years old was introduced in December 2008. However, the national policy does not make provision for individuals aged ≥5 years who have medical conditions associated with a high risk of invasive Hib disease to receive Hib vaccine. We measured serum anti-polyribosylribitol phosphate specific (anti-PRP) antibodies to Hib in patients aged ≥5 years with hematological malignancies and asplenia and evaluated their levels of anti-PRP antibodies in post administration of Hib vaccine era. A total of 65 patients (48 with hematological malignancies, and 17 with asplenia) were included in this study, of which 84% had not received Hib vaccine. In addition, 95.4% had short-term protective levels of anti-PRP antibodies (defined as ≥0.15 µg/mL) and 41.5% had long-term protective levels of anti-PRP antibodies (defined as ≥1.0 µg/mL). Five patients had low anti-PRP antibody levels despite a history of Hib vaccination. Our results suggest that young patients with underlying diseases such as hematological malignancies and asplenia may be at risk of invasive Hib disease. Hence, we recommend they should receive Hib vaccines even if they are over the age limit for routine Hib vaccination program.
Assuntos
Infecções por Haemophilus , Vacinas Anti-Haemophilus , Haemophilus influenzae tipo b , Neoplasias Hematológicas , Anticorpos Antibacterianos , Criança , Pré-Escolar , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/prevenção & controle , Haemophilus influenzae , Humanos , Lactente , Japão/epidemiologia , Polissacarídeos , Vacinas ConjugadasRESUMO
Detecting Pneumocystis jirovecii by bronchoalveolar lavage or lung biopsy is the gold standard for diagnosis of P. jirovecii pneumonia (PJP); however, these techniques are not always applicable in children because of their high invasiveness. We report two pediatric cases of PJP diagnosed by polymerase chain reaction (PCR) of gastric lavage that were successfully treated. To date, there are no reported cases of using PCR of gastric lavage to diagnose PJP. On the day of PJP onset, both the infants required respiratory support and infiltrative shadows were observed in both lung fields on chest radiography. Furthermore, their (1 â 3)-ß-D glucan levels were elevated. P. jirovecii was detected by PCR of gastric lavage and trimethoprim-sulfamethoxazole was administered for 3 weeks, following which their condition improved. They were long-term steroid users, but without any prophylaxis. PCR of gastric lavage in cases of suspected PJP may help in confirming the diagnosis in children who have mild to moderate airway symptoms, or have difficulty with invasive examination like bronchoscopy.
Assuntos
Lavagem Gástrica , Hospedeiro Imunocomprometido , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , DNA Bacteriano/isolamento & purificação , Humanos , Lactente , Recém-Nascido de Peso Extremamente Baixo ao Nascer/imunologia , Recém-Nascido , Recém-Nascido Prematuro/imunologia , Masculino , Pneumocystis carinii/genética , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/microbiologia , Reação em Cadeia da Polimerase , Resultado do TratamentoRESUMO
Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) with aggressive disease characteristics resulting in multiple relapses after initial treatment. Lenalidomide is an immunomodulatory agent approved in the US for patients with relapsed/refractory MCL following bortezomib based on results from 3 multicenter phase II studies (2 including relapsed/refractory aggressive NHL and 1 focusing on MCL post-bortezomib). The purpose of this report is to provide longer follow-up on the MCL-001 study (follow-ups were 6.8 [NHL-002], 7.6 [NHL-003], and 52.2 [MCL-001] months). The 206 relapsed MCL patients treated with single-agent lenalidomide (25 mg/day PO, days 1 to 21 every 28-days) had a median age of 67 years (63% ≥65 years), 91% with stage III/IV disease, and 50% with ≥4 previous treatment regimens. With a median follow-up of X, the combined best overall response rate (ORR) was 33% (including 11% with complete remission [CR]/CR unconfirmed CRu). Lenalidomide produced rapid and durable responses with a median time to response of 2.2 months and median duration of response (DOR) of 16.6 months (95% CI: 11.1%-29.8%). The safety profile was consistent and manageable; myelosuppression was the most common adverse event (AE). Overall, single-agent lenalidomide showed consistent efficacy and safety in multiple phase II studies of heavily pretreated patients with relapsed/refractory MCL, including those previously treated with bortezomib.
Assuntos
Antineoplásicos/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Talidomida/análogos & derivados , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Anemia/epidemiologia , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Estimativa de Kaplan-Meier , Lenalidomida , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Recidiva , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologiaRESUMO
A 16-year-old boy with chronic granulomatous disease presented with pneumonia and rib osteomyelitis. Emericella nidulans var. echinulata was isolated from his sputum. After starting voriconazole, Rasamsonia piperina was isolated from the rib swelling. A combination therapy of voriconazole and micafungin effectively eradicated this invasive mixed-mold infection. In immunocompromised patients, a precise pathogenic diagnosis is clinically useful for administration of an appropriate treatment regimen.
Assuntos
Antifúngicos/uso terapêutico , Ascomicetos/efeitos dos fármacos , Equinocandinas/uso terapêutico , Emericella/efeitos dos fármacos , Doença Granulomatosa Crônica/microbiologia , Lipopeptídeos/uso terapêutico , Micoses/tratamento farmacológico , Micoses/microbiologia , Voriconazol/uso terapêutico , Adolescente , Ascomicetos/isolamento & purificação , Coinfecção/tratamento farmacológico , Emericella/isolamento & purificação , Humanos , Hospedeiro Imunocomprometido , Masculino , Micafungina , Escarro/microbiologiaRESUMO
After introducing the 13-valent pneumococcal conjugate vaccine (PCV13) for children, a change in the prevalence of different Streptococcus pneumoniae serotypes that cause invasive pneumococcal diseases (IPDs) has been observed. The prevalence of vaccine serotypes has decreased and that of non-vaccine serotypes has increased. Currently, serogroup 24 has become one of the major non-vaccine serotypes causing IPDs in children in Japan. The aim of this study was to characterize clinical and genomic features of S. pneumoniae serogroup 24 strains isolated from sterile body sites in Japanese children. Serotyping, multi-locus sequence typing and genomic analysis of capsular polysaccharides of 61 strains of serogroup 24 were performed from 2015 to 2021. Among the 61 strains, 36, 23 and two belonged to serotypes 24F, 24B and 24C, respectively. The 24F sequence type (ST) 2572 and 24B ST 2572 were the major serotypes and sequence types observed from 2015 to 2019. By contrast, 24F ST 162 and 24B ST 2754 were the two major serotypes and sequence types observed after 2020. Two strains of serotype 24C were detected for the first time in Japan. Sequence analysis of the abpA gene, which plays a role in the synthesis of capsular polysaccharides in S. pneumoniae , was performed to distinguish different strains of serogroup 24. After the introduction of PCV13 in Japan, serogroup 24 has become one of the most prevalent non-vaccine serotypes causing IPDs in children. This serogroup has not been targeted in the next-generation pneumococcal conjugate vaccines. Therefore, monitoring of S. pneumoniae serogroup 24 that causes IPDs in children is essential.
RESUMO
The members of the Japanese Society for Pediatric Infectious Diseases and the Japanese Society of Pediatric Pulmonology have developed Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating appropriate diagnosis, treatment and prevention of respiratory infections in children. The first edition was published in 2004 and the fifth edition was published in 2022. The Guideline 2022 consists of 2 parts, clinical questions and commentary, and includes general respiratory infections and specific infections in children with underlying diseases and severe infections. This executive summary outlines the clinical questions in the Guidelines 2022, with reference to the Japanese Medical Information Distribution Service Manual. All recommendations are supported by a systematic search for relevant evidence and are followed by the strength of the recommendation and the quality of the evidence statements.
Assuntos
Doenças Transmissíveis , Infecções Respiratórias , Criança , Humanos , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/terapia , Japão/epidemiologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologiaRESUMO
Streptococcus pneumoniae is one of the leading causes of meningitis in children. In Japan, since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), the number of pneumococcal meningitis due to non-PCV13 serotypes in children has increased. To clarify the clinical outcomes, serotype distributions, and antimicrobial susceptibility of isolated S. pneumoniae strains from pediatric pneumococcal meningitis, we clinically and bacteriologically analyzed 34 cases of pediatric pneumococcal meningitis that were reported after the PCV13 introduction era in Japan. The median age at diagnosis was 1 year (range: 3 months-13 years). Ten (29.4%) patients had underlying diseases. Twenty-nine (85.3%) patients had received at least one dose of any pneumococcal vaccine. Of the 34 patients with pneumococcal meningitis, 6 had sequelae, and 4 died. Nine (26.5%) strains were resistant to penicillin; five (15%) strains to meropenem, with an MIC of 0.5 µg/mL. All strains were susceptible to vancomycin and linezolid. Daptomycin's MIC50 was 0.064 µg/mL and MIC90 was 0.094 µg/mL. Among the tested strains, only four were PCV13 serotypes. Penicillin-resistant S. pneumoniae was isolated from 30.0% of the patients with sequelae and death. Particularly, the proportion of serotype 10A in the sequelae and deceased cases was significantly higher than that in the complete recovery cases. We should carefully monitor the serotype and drug susceptibility of S. pneumoniae strains isolated from patients with meningitis after the PCV13 era and reconsider the treatment strategy to prepare against further drug-resistant pneumococcal strains. IMPORTANCE We analyzed 34 cases of pediatric pneumococcal meningitis that were reported after the 13-valent pneumococcal conjugate vaccine (PCV13) introduction era in Japan. Our study revealed that pneumococcal meningitis in children was mainly caused by non-PCV13 serotypes; all cases with sequelae and death were caused by non-PCV13 serotypes. Moreover, all serotypes of penicillin resistant Streptococcus pneumoniae strains (26.5%; 9/34) were non-PCV13 serotypes. We also analyzed antimicrobial susceptibilities of glycopeptides, linezolid (LZD), and daptomycin (DAP) of isolated S. pneumoniae strains. All tested strains were susceptible to vancomycin, teicoplanin, LZD, and DAP. Especially. DAP demonstrated the best outcome among the tested antibiotics, with MIC90 of 0.094 µg/mL. Pneumococcal meningitis in children continues to persist and is difficult to control with the current conjugate vaccines. Therefore, it is important to monitor the serotype and antimicrobial susceptibility of S. pneumoniae strains isolated from patients with meningitis and accordingly reconsider the treatment strategy.
Assuntos
Daptomicina , Meningite Pneumocócica , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Daptomicina/uso terapêutico , Humanos , Lactente , Japão/epidemiologia , Linezolida/uso terapêutico , Meningite Pneumocócica/tratamento farmacológico , Meningite Pneumocócica/epidemiologia , Meningite Pneumocócica/prevenção & controle , Penicilinas/uso terapêutico , Vacinas Pneumocócicas , Sorogrupo , Streptococcus pneumoniae , Vacinas Conjugadas/uso terapêutico , Vancomicina/uso terapêuticoRESUMO
Hematological malignancy and solid tumor are major risks for invasive pneumococcal disease. Thirteen-valent pneumococcal conjugate vaccine (PCV13) is recommended for immunocompromised patients aged 6 years and older and adults who had not received the vaccine previously. However, vaccination for these individuals is not publicly subsidized in Japan. We measured pneumococcal serotype-specific IgGs (Pn-IgGs) and opsonophagocytic activities (Pn-OPAs) against PCV13 serotypes (1, 3, 5, 6A, 7F, and 19A) in patients with hematological malignancies and solid tumors who were outside the recommended age range for routine vaccination at baseline and at 1 and 6 months after the first dose of PCV13. Pneumococcal serotype-specific memory B cells (Pn-MBCs) against serotype 3 were measured from a portion of the study samples. Thirty-seven patients (30 in the young patient group and 7 in the adult patient group) completed the study. Pn-IgGs were significantly elevated at 1 month post-vaccination and persisted in protection level for 6 months after the first vaccination against all six serotypes measured except serotype 3. Pn-OPAs were significantly elevated and persisted as well against all six serotypes. Pn-MBCs were measured in 10 patients, and 90% of them had at least one detectable Pn-MBC, and 70% of them showed an increased frequency of Pn-MBCs against serotype 3. No serious adverse events were observed up to 1 month after vaccination. PCV13 is thus safe and immunogenic, including against serotype 3, in patients with hematological malignancies and solid tumors outside the recommended age range for routine vaccination.
Assuntos
Neoplasias Hematológicas , Neoplasias , Infecções Pneumocócicas , Anticorpos Antibacterianos , Humanos , Lactente , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/efeitos adversos , Vacinação/efeitos adversos , Vacinas Conjugadas/efeitos adversosRESUMO
Patients with asplenia are at high risks of severe infections caused by encapsulated bacteria, particularly Streptococcus pneumoniae. Thirteen-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) are recommended for invasive pneumococcal disease prevention; however, little is known about the immunity to pneumococci in young patients with asplenia. We measured pneumococcal serotype-specific IgG (Pn-IgG) levels and pneumococcal opsonophagocytic activity (Pn-OPA) against some PCV13-contained serotypes (1, 3, 5, 6A, 7 F, 19A) in 23 young patients with asplenia using surplus serum samples. In this study, 5 and 13 patients had received PCV13 during routine immunizations and PPSV23, respectively; however, >5 years had passed since the last dose in most cases. The geometric mean concentrations (GMCs) of Pn-IgG in all study patients were not under the cutoff level against six serotypes, but they were lower than the those of age-matched healthy controls, as we have previously published. The patients who had received only PPSV23 had significantly lower GMCs against four serotypes (serotypes 1, 6A, 7 F, and 19A) than that of the patients who had received at least one PCV13 vaccination. The patients who had received only PPSV23 also had significantly lower geometric mean titers (GMTs) of Pn-OPA against all three serotypes we measured (serotypes 3, 5, and 19A) than that of the patients who had received at least one PCV13 vaccination. Our findings are useful data that can indicate insufficient immunity in young patients with asplenia against some PCV13 pneumococci serotypes and suggest the need for appropriate vaccinations in the post-PCV13 era.
Assuntos
Anticorpos Antibacterianos , Infecções Pneumocócicas , Humanos , Imunoglobulina G , Japão , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Sorogrupo , Vacinas ConjugadasRESUMO
The pneumococcal conjugate vaccines successfully decreased the incidence of invasive pneumococcal diseases and pneumococcal antibiotic resistance. However, they also led to serotype replacements. According to a report by the National Institute of Infectious Diseases (NIID) in 2017, 96% of pneumococcal isolates obtained from children with IPD aged < 5 years were non-PCV13 serotypes. Here, we report the case of a Japanese immunocompetent and vaccinated child who developed refractory meningitis caused by Streptococcus pneumoniae nonvaccine serotype 10A. PCR revealed genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) with triple mutations (pbp1a + 2b + 2x). Multilocus sequence typing identified the strain as a sequence type (ST) 11189. The ST11189 strain has not been reported in Japan, but it has recently been reported as a cause of invasive infections in Korea. The clinical course was complicated by the development of brain and subdural abscesses that necessitated prolonged antibiotic treatment and multiple burr hole drainages. Unfortunately, the neurological sequelae persisted. Continued molecular surveillance is needed for monitoring emerging virulent clinical strains.
Assuntos
Meningites Bacterianas/diagnóstico , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Farmacorresistência Bacteriana Múltipla , Humanos , Lactente , Meningites Bacterianas/tratamento farmacológico , Tipagem de Sequências Multilocus , Penicilinas/farmacologia , Infecções Pneumocócicas/tratamento farmacológico , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/genéticaRESUMO
Japan has not been able to eliminate rubella; as a result, the large rubella epidemic has occurred. Considering the complicated history of the vaccine policy in Japan, some susceptible populations became infected with rubella, resulting in an outbreak. We conducted a large serosurveillance against rubella in Chiba city after initiating free rubella-specific antibody testing and an immunization campaign during 2018-2019. The total number of rubella specific antibody tests that was conducted in the nationwide campaign and Chiba city original campaign was 8277 and 6104, respectively. The proportion of participants with an antibody titer of ≤1:16 using the hemagglutination inhibition (HI) test was higher in those in their 20-30s. On the contrary, the proportion of participants with an antibody titer of <1:8 using the HI test was higher in men in their 40-50s. This discrepancy possibly reflects the complicated history of the vaccine policy. The number of participants in the nationwide immunization campaign in this city was 1517, whereas that in the Chiba city campaign was 3607. The Chiba city campaign was effective against women in their 20-30s (child-bearing generation); however, the nationwide campaign was not sufficiently effective against men in their 40-50s because many workers were did not visit medical facilities to receive the measles-rubella vaccine.
Assuntos
Sarampo , Rubéola (Sarampo Alemão) , Anticorpos Antivirais , Surtos de Doenças , Feminino , Humanos , Japão , Masculino , Sarampo/epidemiologia , Rubéola (Sarampo Alemão)/epidemiologia , Vacina contra Rubéola , VacinaçãoRESUMO
Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma with a poor prognosis following first relapse. We present a subgroup analysis of an open-label phase II trial investigating the efficacy and safety of lenalidomide in patients with relapsed or refractory MCL. Oral lenalidomide 25 mg was self-administered once daily on days 1-21 every 28 d for up to 52 weeks, according to tolerability or until disease progression. The primary endpoint was overall response rate (ORR) and secondary endpoints were duration of response, progression-free survival (PFS) and safety. Among 15 patients with MCL with a median disease duration of 5.1 years and a median of four prior treatments, the ORR was 53%. Three patients (20%) had a complete response and 5 (33%) had a partial response. The median duration of response was 13.7 months and median PFS was 5.6 months. Four of five patients who relapsed after transplantation and two of five patients who previously received bortezomib responded to lenalidomide. The most common grade 4 adverse event was thrombocytopenia (13%) and the most common grade 3 adverse events were neutropenia (40%), leucopenia (27%) and thrombocytopenia (20%). In conclusion, oral lenalidomide monotherapy is well tolerated and active in relapsed or refractory MCL.
Assuntos
Antineoplásicos/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Talidomida/análogos & derivados , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Estimativa de Kaplan-Meier , Lenalidomida , Leucopenia/induzido quimicamente , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/mortalidade , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Recidiva , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
CC-292, a potent Bruton tyrosine kinase inhibitor, is under development for the treatment of B-cell malignancies. An analysis was performed to develop a population pharmacokinetic model of CC-292 and assess the influence of demographics and disease-related covariates on CC-292 exposure and to assess the exposure-response (overall response rate) relationship in patients with chronic lymphocytic leukemia. Population pharmacokinetic analysis was based on a 2-compartment base model conducted in NONMEM. Categorical exposure-response analysis was performed using logistic regression in SAS. The population pharmacokinetic analysis results indicated that CC-292 pharmacokinetic disposition is similar between healthy subjects and patients. CC-292 showed a larger central compartment volume of distribution than the peripheral compartment volume of distribution (158 L and 72 L, respectively) and a faster clearance than intercompartmental clearance (134 L/h and 18.7 L/h, respectively), indicating that for CC-292, clearance from blood occurs faster than distribution into deep tissues and organs. CC-292 clearance is not affected by demographics or baseline clinical lab factors, except for sex. Although sex significantly reduced variation of apparent clearance, the sex effect on apparent clearance is unlikely to be clinically relevant. The exposure-response analysis suggested that higher drug exposure is linearly correlated with higher overall response rate. A twice-daily dose regimen showed higher overall response rate as compared to once-daily dosing, consistent with a threshold concentration of approximately 300 ng/mL, above which the probability of overall response rate significantly increases.
Assuntos
Acrilamidas/farmacocinética , Antineoplásicos/farmacocinética , Leucemia Linfocítica Crônica de Células B/metabolismo , Modelos Biológicos , Inibidores de Proteínas Quinases/farmacocinética , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/farmacocinética , Acrilamidas/uso terapêutico , Adulto , Tirosina Quinase da Agamaglobulinemia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
Breast involvement with non-Hodgkin's lymphoma (NHL) is rare. Patients with AIDS have an increased incidence of NHL, often with high-grade histology, extranodal presentation and aggressive clinical course. Lymphoma of the breast in patients with HIV-1 infection has not been reported. We reviewed our tumor registry database of all AIDS-associated NHL and report on the clinical presentation and long-term outcome of 3 patients with AIDS who presented with lymphomatous involvement of the breast.
Assuntos
Neoplasias da Mama Masculina/complicações , Neoplasias da Mama/complicações , Infecções por HIV/complicações , Linfoma Relacionado a AIDS/complicações , Linfoma não Hodgkin/complicações , Adulto , Antígenos CD/biossíntese , Neoplasias da Mama/imunologia , Neoplasias da Mama/terapia , Neoplasias da Mama Masculina/imunologia , Neoplasias da Mama Masculina/terapia , Progressão da Doença , Evolução Fatal , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/terapia , Humanos , Linfoma Relacionado a AIDS/imunologia , Linfoma Relacionado a AIDS/terapia , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Resultado do TratamentoRESUMO
Seckel syndrome is a rare autosomal recessive disorder with characteristic craniofacial dysmorphism, skeletal defects, mental and prenatal growth retardation. About 50 cases have been reported in the literature. Hematologic abnormalities with associated chromosomal fragility have been noted in about 15% of the reported cases. We report a patient with Seckel syndrome with myelodysplastic features and clonal T-cells in the bone marrow but no evidence of chromosomal fragility. After 5 years of follow-up, this patient remains asymptomatic without any treatment and with stable peripheral blood counts.
Assuntos
Anormalidades Múltiplas/diagnóstico , Síndromes Mielodisplásicas/diagnóstico , Linfócitos T/imunologia , Adulto , Medula Óssea/patologia , Osso e Ossos/anormalidades , Aberrações Cromossômicas , Células Clonais , Anormalidades Craniofaciais/diagnóstico , Transtornos do Crescimento/diagnóstico , Humanos , Deficiência Intelectual/diagnóstico , Masculino , Síndromes Mielodisplásicas/patologia , SíndromeRESUMO
PURPOSE: The gastrointestinal (GI) tract is the most common site of extranodal disease in patients with systemic non-Hodgkin's lymphoma (NHL). Patients with systemic NHL and GI involvement associated with AIDS (GI-ARL) have a significantly worse prognosis than those without AIDS. We studied whether the introduction of HAART is associated with improved survival in patients with GI-ARL. PATIENTS AND METHOD: 36 patients with GI-ARL were identified from the tumor registries of a large municipal hospital in New York City and a tertiary care facility in western New York State. Of these, 28 patients did not receive HAART and 8 were treated with HAART. The primary endpoint was survival, which was defined as time from date of diagnosis of NHL until death from any cause. RESULTS: Patients were analyzed based on whether or not they were treated with HAART. Kaplan-Meier analysis showed significantly better survival in patients with GI-ARL who were concurrently treated with HAART (p =.014). Median survival was 5 months for the no-HAART group and 30 months for the HAART group. CONCLUSION: In patients with GI-ARL who were treated with chemotherapy, concurrent therapy with HAART therapy was associated with improved survival.