Background. Since 2005, an increase in the prevalence of Clostridium difficile infection (CDI) due to polymerase chain reaction ribotype 078 has been noticed in The Netherlands. This strain has also ...been identified as the predominant strain in pigs and calves. Methods. CDI caused by type 078 was studied in relation to CDI caused by the hypervirulent type 027 and by types other than 027 and 078. Human and porcine isolates were further investigated and characterized by multilocus variable number tandem repeat analysis. Results. From February 2005 through February 2008, the incidence of type 078 among isolates obtained from 1687 patients increased from 3% to 13%. Compared with patients infected with type 027, patients infected with type 078 were younger (67.4 vs. 73.5 years; P×.01) and more frequently had community-associated disease (17.5% vs. 6.7%; odds ratio, 2.98; 95% confidence interval, 2.11–8.02); rates of severe diarrhea (38.9% vs. 40.0%) and attributable mortality (3.8% vs. 4.0%) were similar in both groups. Compared with patients infected with other types, patients infected with type 078 more frequently received fluoroquinolone therapy (29.4% vs. 19.8%; odds ratio, 2.17; 95% confidence interval, 1.06–4.44). Type 078 isolates contained genes for toxin A, toxin B, binary toxin, and a 39–base pair deletion in toxin regulator gene (tcdC), as well as a point mutation at position 184, resulting in a stop codon. Multilocus variable number tandem repeat analysis of 54 human and 11 porcine isolates revealed 4 clonal complexes containing both porcine and human isolates. Conclusions. CDI due to type 078 and CDI due to type 027 present with similar severity, but CDI due to type 078 affects a younger population and is more frequently community associated. C. difficile type 078 isolates from humans and pigs are highly genetically related.
The early epidemiology of the 2022 monkeypox epidemic in non-endemic countries differs substantially from the epidemiology previously reported from endemic countries. We aimed to describe the ...epidemiological and clinical characteristics among individuals with confirmed cases of monkeypox infection.
We descriptively analysed data for patients with confirmed monkeypox who were included in the GeoSentinel global clinical-care-based surveillance system between May 1 and July 1 2022, across 71 clinical sites in 29 countries. Data collected included demographics, travel history including mass gathering attendance, smallpox vaccination history, social history, sexual history, monkeypox exposure history, medical history, clinical presentation, physical examination, testing results, treatment, and outcomes. We did descriptive analyses of epidemiology and subanalyses of patients with and without HIV, patients with CD4 counts of less than 500 cells per mm3 or 500 cells per mm3 and higher, patients with one sexual partner or ten or more sexual partners, and patients with or without a previous smallpox vaccination.
226 cases were reported at 18 sites in 15 countries. Of 211 men for whom data were available, 208 (99%) were gay, bisexual, or men who have sex with men (MSM) with a median age of 37 years (range 18–68; IQR 32–43). Of 209 patients for whom HIV status was known, 92 (44%) men had HIV infection with a median CD4 count of 713 cells per mm3 (range 36–1659; IQR 500–885). Of 219 patients for whom data were available, 216 (99%) reported sexual or close intimate contact in the 21 days before symptom onset; MSM reported a median of three partners (IQR 1–8). Of 195 patients for whom data were available, 78 (40%) reported close contact with someone who had confirmed monkeypox. Overall, 30 (13%) of 226 patients were admitted to hospital; 16 (53%) of whom had severe illness, defined as hospital admission for clinical care rather than infection control. No deaths were reported. Compared with patients without HIV, patients with HIV were more likely to have diarrhoea (p=0·002), perianal rash or lesions (p=0·03), and a higher rash burden (median rash burden score 9 IQR 6–21 for patients with HIV vs median rash burden score 6 IQR 3–14 for patients without HIV; p<0·0001), but no differences were identified in the proportion of men who had severe illness by HIV status.
Clinical manifestations of monkeypox infection differed by HIV status. Recommendations should be expanded to include pre-exposure monkeypox vaccination of groups at high risk of infection who plan to engage in sexual or close intimate contact.
US Centers for Disease Control and Prevention, International Society of Travel Medicine.
Abstract
Background
Patients with hematological cancers (HC) are at high risk of infections, in particular community-acquired pneumonia (CAP). Recent data on incidence and predictors of CAP among ...patients with HC are scarce.
Methods
We performed a cohort study (2016–2019) in 2 hospitals in the Netherlands among adults with HC to calculate incidence rates (IRs) of CAP. In addition, we performed a nested case-control study to identify predictors of CAP.
Results
We identified 275 CAP cases during 6264 patient-years of follow-up. The IR of CAP was 4390/100 000 patient-years of follow-up. Compared with the general population, IR ratios ranged from 5.4 to 55.3 for the different HCs. The case fatality and intensive care unit (ICU) admission rates were 5.5% and 9.8%, respectively. Predictors for CAP in patients with HC were male sex, anemia, lymphocytopenia, chronic kidney disease, cardiovascular disease, autologous and allogeneic stem cell transplantation, treatment with immunosuppressive medication for graft-vs-host disease, treatment with rituximab in the past year, and treatment with immunomodulators (lenalidomide, thalidomide, pomalidomide and/or methotrexate) in the past month. Independent predictors of a severe disease course (death or ICU admission) included neutropenia (odds ratio, 4.14 95% confidence interval, 1.63–10.2), pneumococcal pneumonia (10.24 3.48–30.1), chronic obstructive pulmonary disease (6.90 2.07–23.0), and the use of antibacterial prophylaxis (2.53 1.05–6.08).
Conclusions
The burden of CAP in patients with HC is high, with significant morbidity and mortality rates. Therefore, vaccination against respiratory pathogens early in the disease course is recommended, in particular before starting certain immunosuppressive therapies.
A high burden of community-acquired pneumonia (CAP) was observed in oncohematological patients. Use of rituximab, immunomodulators, and immunosuppressive agents for graft-vs-host disease were the strongest predictors of CAP, highlighting the importance of vaccination against respiratory pathogens before treatment initiation.
•Immunosuppressive agents mitigate the immune response to pneumococcal vaccination.•Anti-TNFα is associated with a better response than DMARDS or combination therapy.•Short-term response to PCV is ...lower than to PPSV when using immunosuppressive drugs.•Uniform definitions of seroconversion and correlates of protection are needed.
Patients with a weakened immune system due to immunosuppressive treatment are at increased risk of infection with Streptococcus pneumoniae. Although pneumococcal vaccination is highly recommended for those patients, the effectiveness of pneumococcal vaccination in this population remains largely unknown. Therefore, the objective of this PROSPERO-registered systematic review and meta-analysis was to evaluate the effect of the most commonly prescribed immunosuppressive agents such as azathioprine, methotrexate, anti-Tumor Necrosis Factor α (TNFα), or rituximab, on the initial serologic response to pneumococcal vaccination in patients with auto-immune disease.
We included 22 articles comprising 2077 patients, of whom 1623 were treated with immunosuppressive agents, and 454 were controls.
The findings of our systematic review indicate that, in patients treated with immunosuppressive medication and compared to controls, the initial serologic response to pneumococcal conjugate vaccine (PCV) and pneumococcal polysaccharide vaccine (PPSV) are impaired. Moreover, this impaired response was more profound after PCV than after PPSV. We hypothesize that the immunosuppressive medication mainly compromises the cellular immunity, explaining the more severely reduced response rate to PCV (which induces a T-cell dependent immune response), compared to PPSV. Treatment with TNFα blocking agents was associated with a more favorable response, compared to patients treated with other immunosuppressive medication. Targeted research applying uniform correlates of protection is needed to bridge the knowledge gap in vaccination immunology in this patient group.
PROSPERO registration: CRD42017058364.
Patients with hematologic conditions have a higher risk of severe COVID-19 and COVID-19-related death. This is related to immune deficiencies induced by hematologic conditions and/or the treatment ...thereof. Prospective vaccine immunogenicity studies have demonstrated that in the majority of patients, a 3-dose COVID-19 vaccination schedule leads to antibody concentrations comparable to levels obtained in healthy adults after a 2-dose schedule. In B cell depleted patients, humoral responses are poor, however vaccination did induce potent cellular immune responses. The effect of 3-dose vaccination schedules and COVID-19 booster vaccinations on the protection of patients with hematologic malignancies against severe COVID-19 and COVID-19 related death remains to be confirmed by population-based vaccine effectiveness studies.
The 2013-16 epidemic of Ebola virus disease in west Africa was a game changer--not only in terms of the location and dimension of the outbreak and with regards to many painful lessons learnt about ...the epidemiology, features, and management of the disease, but also in terms of furthering the development of monoclonal antibody treatments1,2 and, most importantly, vaccines. Besides the replicative vector-based rVSV-ZEBOV vaccine,3,4 which has yielded high efficacy in an interim analysis of an open-label, cluster-randomised ring vaccination trial in Guinea,5 a range of other candidate vaccines have progressed into clinical development.
A trial involving 434 participants examined the effects of no boosting or of boosting with one of the three approved Covid-19 vaccines — Ad26.COV2.S, mRNA-1273, or BNT162b2 — 3 months after the ...primary vaccination. All the vaccines increased neutralizing-antibody levels and T-cell responses, but the increases with the mRNA vaccines were higher.
Non-timely reporting, selective reporting, or non-reporting of clinical trial results are prevalent and serious issues. WHO mandates that summary results be available in registries within 12 months ...of study completion and published in full text within 24 months. However, only a limited number of clinical trials in infectious diseases, including those done during the COVID-19 pandemic, have their results posted on ClinicalTrials.gov. An analysis of 50 trials of eight antiviral drugs tested against COVID-19 with a completion date of at least 2 years ago revealed that only 18% had their results published in the registry, with 40% not publishing any results. Non-timely and non-reporting practices undermine patient participation and are ethically unacceptable. Strategies should include obligatory reporting of summary results within 12 months in clinical trial registries, with progress towards peer-reviewed publication within 24 months indicated. Timely publication of research papers should be encouraged through an automated flagging mechanism in clinical trial registries that draws attention to the status of results reporting, such as a green tick for trials that have reported summary results within 12 months and a red tick in case of failure to do so. We propose the inclusion of mandatory clinical trial reporting standards in the International Conference on Harmonization Good Clinical Practice guidelines, which should prohibit sponsor contract clauses that restrict reporting (referred to as gag clauses) and require timely reporting of results as part of the ethics committees' clearance process for clinical trial protocols.
Zika virus: who's next? Goorhuis, Abraham; Grobusch, Martin P
The Lancet infectious diseases,
11/2016, Letnik:
16, Številka:
11
Journal Article
Recenzirano
Odprti dostop
The potential of Zika virus to spread beyond southern America has been shown in several case series describing imported infections in various countries around the world.1-4 A major concern is whether ...and to what extent these importations will result in subsequent autochthonous transmission of the virus, further fuelling the spread of the epidemic. Because Zika virus is arthropod-borne, transmission depends on the abundance of a competenta aedes mosquito population, which, depending on climatic conditions, can be either year-round or seasonal. Local circulation of Zika virus in southeast Asia was followed by outbreaks in Micronesia,9 French Polynesia, and other Pacific Islands (2013-14), and finally the Americas (2015).10 The similarity to the epidemic spread of another arboviral infection, chikungunya, is striking. ...the identification of an outbreak on Réunion Island in 2005, chikungunya was also a neglected disease, despite its widespread presence.
PDF
