Time Until Partial Response in Metastatic Adrenocortical Carcinoma Long-Term Survivors

A partial response (PR) has been proposed as a surrogate for overall survival in advanced adrenocortical carcinoma (ACC). The primary endpoint of the study was to characterize the time until a PR in patients with metastatic ACC treated with a standard therapy is achieved. Long-term survivors were selected to allow evaluation of delayed tumor response to mitotane. Records from patients with metastatic ACC that survived for > 24 months were retrieved. Tumor response was analyzed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Time until a tumor response, after treatment initiation or therapeutic plasma mitotane level, was analyzed. Sixty-eight patients were analyzed. The first-line systemic therapy was mitotane as a monotherapy (M) (n = 57) or cytotoxic polychemotherapy plus/minus mitotane (PC ± M) (n = 11). The second-line therapy was M (n = 2) or PC ± M (n = 41). Thirty-two PRs occurred in 30/68 patients (44.1%): this was obtained for 13 (40.6%) during M and during PC ± M for 19/32 responders (59.4%). PRs were observed within 6 months of starting M or PC ± M in 76.9 and 94.7% of responses, respectively, within 6 months of therapeutic plasma mitotane being first observed in 88.9% of responses with M and in 53.3% of responses with PC ± M. All PRs (but one) occurred within 1 year after initiating treatment. To conclude, Most patients with metastatic ACC and long survival times had PRs within the first 6 months of standard systemic therapy, and almost all within the first year. The absence of response after that period could be considered as a treatment failure. Maintenance of mitotane therapy in non-responders after 1 year should be questioned in future randomized trials

Risk Factors for Marburg Hemorrhagic Fever, Democratic Republic of the Congo

We conducted two antibody surveys to assess risk factors for Marburg hemorrhagic fever in an area of confirmed Marburg virus transmission in the Democratic Republic of the Congo. Questionnaires were administered and serum samples tested for Marburg-specific antibodies by enzyme-linked immunosorbent assay. Fifteen (2%) of 912 participants in a general village cross-sectional antibody survey were positive for Marburg immunoglobulin G antibody. Thirteen (87%) of these 15 were men who worked in the local gold mines. Working as a miner (odds ratio [OR] 13.9, 95% confidence interval [CI] 3.1 to 62.1) and receiving injections (OR 7.4, 95% CI 1.6 to 33.2) were associated with a positive antibody result. All 103 participants in a targeted antibody survey of healthcare workers were antibody negative. Primary transmission of Marburg virus to humans likely occurred via exposure to a still unidentified reservoir in the local mines. Secondary transmission appears to be less common with Marburg virus than with Ebola virus, the other known filovirus

Prognostic factors in stage III-IV adrenocortical carcinomas (ACC): an European Network for the Study of Adrenal Tumor (ENSAT) study.

BACKGROUND: The clinical course of advanced adrenocortical carcinoma (ACC) is heterogeneous. Our study aimed primarily to refine and make headway in the prognostic stratification of advanced ACC. PATIENTS AND METHODS: Patients with advanced ENSAT ACC (stage III or stage IV) at diagnosis registered between 2000 and 2009 in the ENSAT database were enrolled. The primary end point was overall survival (OS). Parameters of potential prognostic relevance were selected. Univariate and multivariate analyses were carried out: model 1 'before surgery'; model 2 'post-surgery'. RESULTS: Four hundred and forty-four patients with advanced ENSAT ACC (stage III: 210; stage IV: 234) were analyzed. After a median follow-up of 55.2 months, the median OS was 24 months. A modified ENSAT (mENSAT) classification was validated: stage III (invasion of surrounding tissues/organs or the vena renalis/cava) and stage IVa, IVb, IVc (2, 3 or >3 metastatic organs, including N, respectively). Two- or 5-year OS was 73%, 46%, 26% and 15% or 50%, 15%, 14% and 2% for stages III, IVa, IVb and IVc, respectively. In the multivariate analysis, mENSAT stages (stages IVa, IVb, or IVc, respectively) were significantly correlated with OS (P 6 and/or Ki67 ≥20%, P = 0.06) in model 2. CONCLUSION: The mENSAT classification and GRAS parameters (Grade, R status, Age and Symptoms) were found to best stratify the prognosis of patients with advanced ACC

Human plague: An old scourge that needs new answers

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague’s resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a “One Health” approach

Development and Evaluation of Two Simple, Rapid Immunochromatographic Tests for the Detection of Yersinia pestis Antibodies in Humans and Reservoirs

Plague is due to the bacterium Yersinia pestis. It is accidentally transmitted to humans by the bite of infected fleas. Currently, approximately 20 developing countries with very limited infrastructure are still affected. A plague case was defined according to clinical, epidemiological and biological features. Rapid diagnosis and surveillance of the disease are essential for its control. Indeed, the delay of treatment is often rapidly fatal for patients and outbreaks may occur. Bubo aspirate is the most appropriate specimen in case of bubonic plague, but its collection is not always feasible. The main current biological approaches for the diagnosis of human plague are F1 antigen detection, serology for antibody detection by ELISA and Y. pestis isolation. The biological diagnosis of plague remains a challenge because the clinical signs are not specific. In this study, we developed some simple, rapid and affordable tests able to detect specific plague antibodies. These tests can be used as alternative methods for plague diagnosis in the field and for plague surveillance

Detection of infectious disease outbreaks in twenty-two fragile states, 2000-2010: a systematic review.

Fragile states are home to a sixth of the world's population, and their populations are particularly vulnerable to infectious disease outbreaks. Timely surveillance and control are essential to minimise the impact of these outbreaks, but little evidence is published about the effectiveness of existing surveillance systems. We did a systematic review of the circumstances (mode) of detection of outbreaks occurring in 22 fragile states in the decade 2000-2010 (i.e. all states consistently meeting fragility criteria during the timeframe of the review), as well as time lags from onset to detection of these outbreaks, and from detection to further events in their timeline. The aim of this review was to enhance the evidence base for implementing infectious disease surveillance in these complex, resource-constrained settings, and to assess the relative importance of different routes whereby outbreak detection occurs.We identified 61 reports concerning 38 outbreaks. Twenty of these were detected by existing surveillance systems, but 10 detections occurred following formal notifications by participating health facilities rather than data analysis. A further 15 outbreaks were detected by informal notifications, including rumours.There were long delays from onset to detection (median 29 days) and from detection to further events (investigation, confirmation, declaration, control). Existing surveillance systems yielded the shortest detection delays when linked to reduced barriers to health care and frequent analysis and reporting of incidence data.Epidemic surveillance and control appear to be insufficiently timely in fragile states, and need to be strengthened. Greater reliance on formal and informal notifications is warranted. Outbreak reports should be more standardised and enable monitoring of surveillance systems' effectiveness

Risk Factors for Nipah Virus Encephalitis in Bangladesh1

Patients in Goalando were likely infected by direct contact with fruit bats or their secretions, rather than through contact with an intermediate host

Evidence of Yersinia pestis DNA from fleas in an endemic plague area of Zambia

BACKGROUND: Yersinia pestis is a bacterium that causes plague which infects a variety of mammals throughout the world. The disease is usually transmitted among wild rodents through a flea vector. The sources and routes of transmission of plague are poorly researched in Africa, yet remains a concern in several sub-Saharan countries. In Zambia, the disease has been reported on annual basis with up to 20 cases per year, without investigating animal reservoirs or vectors that may be responsible in the maintenance and propagation of the bacterium. In this study, we undertook plague surveillance by using PCR amplification of the plasminogen activator gene in fleas. FINDINGS: Xenopsylla species of fleas were collected from 83 rodents trapped in a plague endemic area of Zambia. Of these rodents 5 had fleas positive (6.02%) for Y. pestis plasminogen activator gene. All the Y. pestis positive rodents were gerbils. CONCLUSIONS: We conclude that fleas may be responsible in the transmission of Y. pestis and that PCR may provide means of plague surveillance in the endemic areas of Zambia