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[This corrects the article DOI: 10.1371/journal.pmed.1003979.].
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BACKGROUND: Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH. METHODS AND FINDINGS: We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S vaccines in adult PLWH without prior COVID-19, and compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response, and reactogenicity. Between 14 February and 7 September 2021, 1,154 PLWH (median age 53 [IQR 44-60] years, 85.5% male) and 440 controls (median age 43 [IQR 33-53] years, 28.6% male) were included in the final analysis. Of the PLWH, 884 received BNT162b2, 100 received mRNA-1273, 150 received ChAdOx1-S, and 20 received Ad26.COV2.S. In the group of PLWH, 99% were on antiretroviral therapy, 97.7% were virally suppressed, and the median CD4+ T-cell count was 710 cells/µL (IQR 520-913). Of the controls, 247 received mRNA-1273, 94 received BNT162b2, 26 received ChAdOx1-S, and 73 received Ad26.COV2.S. After mRNA vaccination, geometric mean antibody concentration was 1,418 BAU/mL in PLWH (95% CI 1322-1523), and after adjustment for age, sex, and vaccine type, HIV status remained associated with a decreased response (0.607, 95% CI 0.508-0.725, p < 0.001). All controls receiving an mRNA vaccine had an adequate response, defined as >300 BAU/mL, whilst in PLWH this response rate was 93.6%. In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+ T-cell count 250-500 cells/µL (2.845, 95% CI 1.876-4.314, p < 0.001) or >500 cells/µL (2.936, 95% CI 1.961-4.394, p < 0.001), whilst a viral load > 50 copies/mL was associated with a reduced response (0.454, 95% CI 0.286-0.720, p = 0.001). Increased IFN-γ, CD4+ T-cell, and CD8+ T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation-induced marker assays, comparable to controls. Reactogenicity was generally mild, without vaccine-related serious adverse events. Due to the control of vaccine provision by the Dutch National Institute for Public Health and the Environment, there were some differences between vaccine groups in the age, sex, and CD4+ T-cell counts of recipients. CONCLUSIONS: After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH compared to HIV-negative controls. To reach and maintain the same serological responses as HIV-negative controls, additional vaccinations are probably required. TRIAL REGISTRATION: The trial was registered in the Netherlands Trial Register (NL9214). https://www.trialregister.nl/trial/9214.
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Vacunas contra la COVID-19 , COVID-19 , Infecciones por VIH , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ad26COVS1 , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Infecciones por VIH/inmunología , Inmunogenicidad Vacunal , Inmunoglobulina G , Países Bajos/epidemiología , Estudios Prospectivos , ARN Mensajero , SARS-CoV-2 , Vacunas de ARNmRESUMEN
Background: Treatment of staphylococcal prosthetic joint infection (PJI) usually consists of surgical debridement and prolonged rifampicin combination therapy. Tailored antimicrobial treatment alternatives are needed due to frequent side effects and drug-drug interactions with rifampicin combination therapy. We aimed to assess the effectiveness of several alternative antibiotic strategies in patients with staphylococcal PJI. Methods: In this prospective, multicenter registry-based study, all consecutive patients with a staphylococcal PJI, treated with debridement, antibiotics and implant retention (DAIR) or 1-stage revision surgery between January 1, 2015 and November 3, 2020, were included. Patients were treated with a long-term rifampicin combination strategy (in 2 centers) or a short-term rifampicin combination strategy (in 3 centers). Antimicrobial treatment strategies in these centers were defined before the start of the registry. Patients were stratified in different groups, depending on the used antimicrobial strategy. Cox proportional hazards models were used to compare outcome between the groups. Results: Two hundred patients were included and stratified in 1 long-term rifampicin group (traditional rifampicin combination therapy) or 1 of 3 short-term rifampicin groups (clindamycin or flucloxacillin or vancomycin monotherapy, including rifampicin for only 5 postoperative days). Adjusted hazard ratios (aHRs) for failure in patients treated with short-term rifampicin and either flucloxacillin or clindamycin were almost equal to patients treated with long-term rifampicin combination therapy (aHR = 1.21; 95% confidence interval, .34-4.40). Conclusions: A short-term rifampicin strategy with either clindamycin or flucloxacillin and only 5 days of rifampicin was found to be as effective as traditional long-term rifampicin combination therapy. A randomized controlled trial is needed to further address efficacy and safety of alternative treatment strategies for staphylococcal PJI.
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INTRODUCTION: Brucella is a genus of aerobic Gram negative bacteria that causes the disease brucellosis. It is considered a zoonotic infection transmitted to humans by ingestion of unpasteurised dairy products. Although aortic involvement is rarely seen, it can be a life threatening complication of this disease. This case report describes a ruptured aneurysm of the common iliac artery (CIA) due to secondary infection by Brucella melitensis. REPORT: A 79 year old man with a known isolated aneurysm of the CIA presented with acute abdominal pain. Contrast enhanced computed tomography (CT) revealed rupture of the aneurysm. The patient underwent prompt endovascular repair. Several weeks after an uneventful recovery, the patient presented with spiking fever and abdominal discomfort. CT revealed an abscess anterior to the CIA. Blood and pus cultures grew B. melitensis. In recurrent re-admissions, conservative antibiotic therapy proved to be insufficient. Eventually, neo-aorto-iliac system (NAIS) reconstruction using bilateral femoral veins was performed to provide definitive treatment four months after initial presentation. CONCLUSION: Although Brucella infected aneurysms are rare, they are associated with life threatening disease. Diagnosing this type of brucellar infection can be challenging owing to the long incubation time needed for blood and tissue cultures. Definitive treatment of these aneurysms often needs open surgery and antibiotics for complete treatment. Vigilant surveillance is required to monitor for post-operative complications such as graft infection, recurrent (false) aneurysm, and abscess formation.
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Nitrofurantoin is a commonly prescribed antibiotic for uncomplicated urinary tract infections. The Dutch College of General Practitioners guideline recommends the use of this drug for the treatment of uncomplicated urinary tract infections in both male and female patients. Treatment with nitrofurantoin has several advantages. Resistance to this antibiotic is low and does not increase in the hospitalized patient population. Treatment with nitrofurantoin is generally well-tolerated. However, two independent studies estimated that approximately 27% of male patients are undertreated with nitrofurantoin. The main downside of nitrofurantoin is the low blood concentration that leads to insufficient tissue penetration. There is little evidence on how often prostatic tissues are involved in male urinary tract infections. Unrecognized tissue involvement can lead to breakthrough urinary tract infections despite nitrofurantoin treatment. Because of this, the safety of nitrofurantoin for male patients is unknown and treatment with this antibiotic should be administered with caution.
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Antiinfecciosos Urinarios/uso terapéutico , Nitrofurantoína/uso terapéutico , Enfermedades de la Próstata/tratamiento farmacológico , Infecciones Urinarias/tratamiento farmacológico , Toma de Decisiones Clínicas , Humanos , Masculino , Selección de Paciente , Enfermedades de la Próstata/microbiología , Infecciones Urinarias/microbiologíaRESUMEN
OBJECTIVES: To investigate the incidence and risk factors of immune reconstitution inflammatory syndrome (IRIS) associated with toxoplasmic encephalitis (TE) in patients starting combination antiretroviral therapy (cART). DESIGN: A historical multicenter cohort study. METHODS: We included all HIV-infected patients diagnosed with toxoplasmic encephalitis in six Dutch hospitals between 1996 and 2016. Diagnosis of TE-IRIS was made using predefined IRIS criteria. We distinguished paradoxical TE-IRIS (worsening of underlying treated infection) from unmasking TE-IRIS (unmasking of subclinical infection after start of cART). We compared CD4 cell count, plasma viral load and timing of cART initiation between patients with and without paradoxical TE-IRIS. RESULTS: A total of 211 toxoplasmic encephalitis cases were included. Among 143 cases at risk for paradoxical TE-IRIS, we identified five cases of paradoxical TE-IRIS (3.5%). In six other cases, we could not differentiate paradoxical TE-IRIS from recurrence of disease due to inadequate secondary Toxoplasma prophylaxis. There was no difference in time between start of toxoplasmic encephalitis treatment and cART initiation for patients who did or did not develop paradoxical TE-IRIS (Pâ=â0.50). Within the group of 2228 patients who started cART while having a CD4 cell count below 200â×â10 cells/l and receiving adequate primary prophylaxis, we identified eight cases of unmasking TE-IRIS (0.36%). Unmasking TE-IRIS could not be differentiated from a newly occurring toxoplasmic encephalitis in six other patients, as they were not receiving adequate primary prophylaxis against Toxoplasma. CONCLUSION: Unmasking TE-IRIS was rare in this cohort, whereas paradoxical TE-IRIS did occur more often. We found no relationship between the timing of cART initiation and the occurrence of paradoxical TE-IRIS.
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Encefalitis/diagnóstico , Encefalitis/patología , Infecciones por VIH/complicaciones , Síndrome Inflamatorio de Reconstitución Inmune/epidemiología , Síndrome Inflamatorio de Reconstitución Inmune/etiología , Toxoplasmosis Cerebral/diagnóstico , Toxoplasmosis Cerebral/patología , Adulto , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/patología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Carga ViralRESUMEN
Notification of 2 imported cases of infection with Middle East respiratory syndrome coronavirus in the Netherlands triggered comprehensive monitoring of contacts. Observed low rates of virus transmission and the psychological effect of contact monitoring indicate that thoughtful assessment of close contacts is prudent and must be guided by clinical and epidemiologic risk factors.
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Trazado de Contacto , Infecciones por Coronavirus/epidemiología , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Infecciones del Sistema Respiratorio/epidemiología , Viaje , Adolescente , Adulto , Anciano , Niño , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Infecciones del Sistema Respiratorio/prevención & control , Infecciones del Sistema Respiratorio/virología , Arabia Saudita , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Immunocompromised patients are extra sensitive to serious influenza infections. A compromised immune system in these patients also results in an impaired immune response following influenza vaccination. Recently, many vaccination studies have been carried out in patients with HIV, patients treated with rituximab or a tumour necrosis factor (TNF)-alpha blocker, patients with malignancies, and in patients following allogeneic stem cell transplantation for haematological malignancy or following solid organ transplantation. In most patient groups influenza vaccination induces a sufficiently high antibody titre. Patients using rituximab, patients who recently received a stem cell transplantation and patients treated with active cytotoxic chemotherapy may show an insufficient antibody response following influenza vaccination. In general, adapted vaccination strategies such as repeated administration of a vaccine or administering a higher dose of vaccine antigen results in a better immune response following vaccination.- Therefore, influenza vaccination is recommended for all patient groups.
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Formación de Anticuerpos/inmunología , Huésped Inmunocomprometido , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Neoplasias Hematológicas/inmunología , Trasplante de Células Madre Hematopoyéticas , Humanos , Neoplasias/inmunología , Vacunación/efectos adversosRESUMEN
BACKGROUND: The immunogenicity of 2009 pandemic influenza A(H1N1) (pH1N1) vaccines and the effect of previous influenza vaccination is a matter of current interest and debate. We measured the immune response to pH1N1 vaccine in HIV-infected patients and in healthy controls. In addition we tested whether recent vaccination with seasonal trivalent inactivated vaccine (TIV) induced cross-reactive antibodies to pH1N1. (clinicaltrials.gov Identifier:NCT01066169). METHODS AND FINDINGS: In this single-center prospective cohort study MF59-adjuvanted pH1N1 vaccine (Focetria®, Novartis) was administered twice to 58 adult HIV-infected patients and 44 healthy controls in November 2009 (day 0 and day 21). Antibody responses were measured at baseline, day 21 and day 56 with hemagglutination-inhibition (HI) assay. The seroprotection rate (defined as HI titers ≥ 1 : 40) for HIV-infected patients was 88% after the first and 91% after the second vaccination. These rates were comparable to those in healthy controls. Post-vaccination GMT, a sensitive marker of the immune competence of a group, was lower in HIV-infected patients. We found a high seroprotection rate at baseline (31%). Seroprotective titers at baseline were much more common in those who had received 2009-2010 seasonal TIV three weeks prior to the first dose of pH1N1 vaccine. Using stored serum samples of 51 HIV-infected participants we measured the pH1N1 specific response to 2009-2010 seasonal TIV. The seroprotection rate to pH1N1 increased from 22% to 49% after vaccination with 2009-2010 seasonal TIV. Seasonal TIV induced higher levels of antibodies to pH1N1 in older than in younger subjects. CONCLUSION: In HIV-infected patients on combination antiretroviral therapy, with a median CD4+ T-lymphocyte count above 500 cells/mm(3), one dose of MF59-adjuvanted pH1N1 vaccine induced a high seroprotection rate comparable to that in healthy controls. A second dose had a modest additional effect. Furthermore, seasonal TIV induced cross-reactive antibodies to pH1N1 and this effect was more pronounced in older subjects.
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Formación de Anticuerpos , Infecciones por VIH/inmunología , Infecciones por VIH/terapia , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Adulto , Anticuerpos Antivirales/sangre , Terapia Antirretroviral Altamente Activa , Linfocitos T CD4-Positivos/inmunología , Estudios de Casos y Controles , Femenino , Infecciones por VIH/complicaciones , Humanos , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/complicaciones , Gripe Humana/prevención & control , Masculino , Persona de Mediana Edad , PandemiasRESUMEN
OBJECTIVE: To prospectively assess the diagnostic utility of S-adenosylmethionine (AdoMet) and (1â3)-ß-D-glucan (ß-D-glucan) serum markers for Pneumocystis pneumonia (PCP) in HIV-negative patients. METHODS: HIV-negative, immunocompromised patients suspected of PCP based on clinical presentation and chest imaging were included. PCP was confirmed or rejected by results of direct microscopy and/or real-time PCR on broncho-alveolar lavage (BAL) fluid. Measurement of serum ß-D-glucan and AdoMet was performed on serum samples collected at enrollment and during follow-up. Both serum ß-D-glucan and AdoMet were assessed for diagnostic accuracy and correlation with clinical and laboratory parameters. RESULTS: In 31 patients enrolled (21 PCP-positive, 10 PCP-negative), AdoMet levels did not discriminate between patients with and without PCP. Elevated serum ß-D-glucan was a reliable indicator for PCP with a sensitivity of 0.90 and specificity of 0.89 at the 60 pg/ml cut-off. In PCP-positive patients ß-D-glucan serum levels decreased during treatment and inversely correlated with Pneumocystis PCR cycle threshold values in BAL fluid. CONCLUSIONS: The level of ß-D-glucan--but not AdoMet--was diagnostic for PCP within the clinical context and may serve as marker for pulmonary fungal load and treatment monitoring.
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Neumonía por Pneumocystis/diagnóstico , S-Adenosilmetionina/sangre , beta-Glucanos/sangre , Anciano , Biomarcadores/sangre , Femenino , Seronegatividad para VIH , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Pneumocystis carinii/aislamiento & purificación , Neumonía por Pneumocystis/sangre , Neumonía por Pneumocystis/inmunología , Estudios Prospectivos , Proteoglicanos , Sensibilidad y EspecificidadAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/metabolismo , Fármacos Anti-VIH/farmacocinética , VIH-2/efectos de los fármacos , Pirrolidinonas/farmacocinética , Tuberculosis/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Adulto , Fármacos Anti-VIH/administración & dosificación , Antibióticos Antituberculosos/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Pirrolidinonas/administración & dosificación , Raltegravir Potásico , Rifampin/administración & dosificación , Tuberculosis/inmunologíaRESUMEN
DESIGN: Rabies vaccine was used as a T-cell-dependent neoantigen to investigate several aspects of the primary and booster immune response in vivo in HIV-infected individuals receiving antiretroviral treatment. METHODS: Study participants received rabies vaccination twice, within a 3-month interval. Serum samples were taken before and 1, 2 and 4 weeks after both vaccinations and 1 and 5 years after the primary vaccination. Antirabies antibodies [immunoglobulin G (IgG), IgG subclasses, immunoglobulin A (IgA) and immunoglobulin M (IgM)] were determined; antibody avidity was measured after both vaccinations. T-cell subsets were characterized by flow cytometry. RESULTS: Eighteen healthy controls and 30 HIV-infected adults, treated with HAART for almost 4 years, with a median CD4(+) T-cell count of 537 cells/microl, were immunized. The postvaccination concentrations of antirabies IgG and IgM were significantly lower in HIV-infected individuals as compared with controls. Three T-cell-dependent processes, a true booster response, a class switch from IgM to IgG and avidity maturation were present in both healthy controls and HIV-infected individuals. Higher age was associated with lower postvaccination antirabies IgG and IgM titers. Five years after the primary vaccination, 63% of the HIV-infected individuals still had antibody titers above the protection threshold. CONCLUSION: Immune restoration in HIV-infected individuals treated with HAART, resulting in a CD4(+) T-cell count greater than 500 cells/microl, is incomplete. However, the majority of HIV-infected individuals are capable of mounting a long-lasting immune response, including several pivotal T-cell-dependent processes, upon vaccination with a neoantigen such as the rabies vaccine.
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Anticuerpos Antivirales/inmunología , Formación de Anticuerpos/fisiología , Infecciones por VIH/inmunología , VIH-1/inmunología , Vacunas Antirrábicas/administración & dosificación , Adulto , Anciano , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , Linfocitos T CD4-Positivos , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Vacunas Antirrábicas/inmunología , Carga Viral , Adulto JovenRESUMEN
Haemophilus influenzae is a rare causative organism of vertebral osteomyelitis in an adult. Cases reported in the literature were mainly caused by ampicillin-susceptible type b strains. Here we describe the first case of vertebral osteomyelitis due to a non-typeable, beta-lactamase low-level ampicillin-resistant H. influenzae strain with failure of prolonged intravenous amoxicillin treatment.
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Amoxicilina/uso terapéutico , Resistencia a la Ampicilina , Antibacterianos/uso terapéutico , Infecciones por Haemophilus/tratamiento farmacológico , Haemophilus influenzae/efectos de los fármacos , Osteomielitis/tratamiento farmacológico , beta-Lactamasas/biosíntesis , Anciano , Infecciones por Haemophilus/microbiología , Haemophilus influenzae/enzimología , Haemophilus influenzae/aislamiento & purificación , Humanos , Masculino , Osteomielitis/microbiología , Insuficiencia del TratamientoRESUMEN
BACKGROUND: An outbreak of Pneumocystis jiroveci pneumonia (PCP) occurred among renal transplant recipients attending the outpatient department at the Leiden University Medical Centre (Leiden, The Netherlands) from 1 March 2005 through 1 February 2006. Clinical, epidemiological, and molecular data were analyzed to trace the outbreak's origin. METHODS: Renal transplant recipients with a clinical suspected diagnosis of PCP were included in the study. The diagnosis had to be confirmed by direct microscopy or real-time polymerase chain reaction of the dihydropteroate synthase gene in a bronchoalveolar fluid specimen. To detect contacts between patients, a transmission map was constructed. A case-control analysis was performed to asses whether infection was associated with certain wardrooms. Genotyping of Pneumocystis isolates was performed by sequence analysis of the internal transcribed spacer (ITS) number 1 and 2 gene regions. RESULTS: Twenty-two confirmed PCP cases were identified; approximately 0-1 would have been expected over the same time period. No risk factor was predominantly present, and standard immunosuppressive regimens had not changed. Liver transplant recipients who used the same outpatient facilities had not acquired PCP. The transmission map findings were compatible with interhuman transmission on multiple occasions. The case-control study did not point to wardrooms as a common source. Genotyping by sequencing of the ITS1 and ITS2 gene regions revealed type Ne in 12 of 16 successfully typed samples. Genotype Ne was found in only 2 of 12 reference samples. CONCLUSIONS: The clinical data and genotyping results are compatible with either interhuman transmission or an environmental source of infection. More complex models may account for PCP clusters.