Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (IMPAMEL II).

BACKGROUND: Treatment of late-stage human African trypanosomiasis (HAT) with melarsoprol can be improved by shortening the regimen. A previous trial demonstrated the safety and efficacy of a 10-day treatment schedule. We demonstrate the effectiveness of this schedule in a noncontrolled, multinational drug-utilization study. METHODS: A total of 2020 patients with late-stage HAT were treated with the 10-day melarsoprol schedule in 16 centers in 7 African countries. We assessed outcome on the basis of major adverse events and the cure rate after treatment and during 2 years of follow-up. RESULTS: The cure rate 24 h after treatment was 93.9%; 2 years later, it was 86.2%. However, 49.3% of patients were lost to follow-up. The overall fatality rate was 5.9%. Of treated patients, 8.7% had an encephalopathic syndrome that was fatal 45.5% of the time. The rate of severe bullous and maculopapular eruptions was 0.8% and 6.8%, respectively. CONCLUSIONS: The 10-day treatment schedule was well implemented in the field and was effective. It reduces treatment duration, drug amount, and hospitalization costs per patient, and it increases treatment-center capacity. The shorter protocol has been recommended by the International Scientific Council for Trypanosomiasis Research and Control for the treatment of late-stage HAT caused by Trypanosoma brucei gambiense

Escherichia coli K88 adhesion: A comparison of Chinese and Large White piglets

A comparative trial was performed on 15 Large White and 12 Chinese germ-free, colostrumdeprived piglets, maintained in plastic film isolators. Shortly after successive oral inoculations of 2 E. coli strains, one K88-positive and one K88-negative, the piglets were sacrificed and bacterial numerations of the 2 strains were done on 3 different intestinal segments of each pig, using both the lumen content and the washed intestinal wall. The percentage of bacteria specifically bound to the intestinal wall was estimated, and the presence or absence of the piglet K88 intestinal receptor was thus inferred. The results tended to indicate that the 12 Chinese piglets lacked this receptor, as against 7 Large White’s. This raises the question of possible breed differences in resistance to this type of colibacillosis.Un essai comparatif a été réalisé sur 15 porcelets Large White et 12 porcelets Chinois, prélevés à la naissance de manière axénique, privés de colostrum et placés en isolateur sous film plastique. Après inoculation par voie orale de 2 souches de E. coli, l’une possédant l’antigène d’attachement K88 (K88+)l’autre dépourvue de cet antigène (K88-), les porcelets sont sacrifiés et 3 segments différents de l’intestin grêle sont prélevés sur chaque porcelet en vue de numérations des 2 souches bactériennes, à la fois dans le contenu intestinal et sur la paroi. Le pourcentage de bactéries spécifiquement attachées à la paroi est ainsi estimé et la présence ou l’absence chez le porcelet du récepteur intestinal K88 peut en être déduite. Les résultats indiquent que les 12 porcelets Chinois ne possèdent pas ce récepteur et doivent donc être résistants à l’attachement de K88, contre 7 porcelets Large White. Cela soulève la question de l’existence possible de races résistantes à cette colibacillose

Rapid Diagnostic Tests for Non-Malarial Febrile Illness in the Tropics

The recent roll-out of rapid diagnostic tests (RDTs) for malaria has highlighted the decreasing proportion of malaria-attributable illness in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of severe febrile illnesses in low resource settings. This review summarizes the current state of RDT development for several key infections, including dengue fever, enteric fever, leptospirosis, brucellosis, visceral leishmaniasis and human African trypanosomiasis, and highlights many remaining gaps. Most RDTs for non-malarial tropical infections currently rely on the detection of host antibodies against a single infectious agent. The sensitivity and specificity of host-antibody detection tests are both inherently limited. Moreover, prolonged antibody responses to many infections preclude the use of most serological RDTs for monitoring response to treatment and/or for diagnosing relapse. Considering these limitations, there is a pressing need for sensitive pathogen-detection-based RDTs, as have been successfully developed for malaria and dengue. Ultimately, integration of RDTs into a validated syndromic approach to tropical fevers is urgently needed. Related research priorities are to define the evolving epidemiology of fever in the tropics, and to determine how combinations of RDTs could be best used to improve the management of severe and treatable infections requiring specific therapy

Machine learning-based lifetime breast cancer risk reclassification compared with the BOADICEA model: impact on screening recommendations

BACKGROUND: The clinical utility of machine-learning (ML) algorithms for breast cancer risk prediction and screening practices is unknown. We compared classification of lifetime breast cancer risk based on ML and the BOADICEA model. We explored the differences in risk classification and their clinical impact on screening practices. METHODS: We used three different ML algorithms and the BOADICEA model to estimate lifetime breast cancer risk in a sample of 112,587 individuals from 2481 families from the Oncogenetic Unit, Geneva University Hospitals. Performance of algorithms was evaluated using the area under the receiver operating characteristic (AU-ROC) curve. Risk reclassification was compared for 36,146 breast cancer-free women of ages 20-80. The impact on recommendations for mammography surveillance was based on the Swiss Surveillance Protocol. RESULTS: The predictive accuracy of ML-based algorithms (0.843 </= AU-ROC </= 0.889) was superior to BOADICEA (AU-ROC = 0.639) and reclassified 35.3% of women in different risk categories. The largest reclassification (20.8%) was observed in women characterised as 'near population' risk by BOADICEA. Reclassification had the largest impact on screening practices of women younger than 50. CONCLUSION: ML-based reclassification of lifetime breast cancer risk occurred in approximately one in three women. Reclassification is important for younger women because it impacts clinical decision- making for the initiation of screening

Set-up of a population-based familial breast cancer registry in Geneva, Switzerland: validation of first results

Background: This article evaluates the accuracy of family history of breast and ovarian cancer among first-degree relatives of breast cancer patients, retrospectively collected during the setting up of a population-based family breast cancer registry. Patients and methods: Family histories of cancer for all women with breast cancer recorded at the Geneva Cancer Registry from 1990 to 1999 were retrospectively extracted from medical files. The accuracy of these family histories was validated among Swiss women born in Geneva: all 119 with a family history of breast (n = 110) or ovarian (n = 9) cancer and a representative sample of 100 women with no family history of breast or ovarian cancer. We identified the first-degree relatives of these women with information from the Cantonal Population Office. All first-degree relatives, resident in Geneva from 1970 to 1999, were linked to the cancer registry database for breast and ovarian cancer occurrence. Sensitivity, specificity and level of overall agreement (κ) were calculated. Results: Among 310 first-degree relatives identified, 61 had breast cancer and six had ovarian cancer recorded at the Geneva Cancer Registry. The sensitivity, specificity and κ of the reported family histories of breast cancer were 98%, 97% and 0.97, respectively. For ovarian cancer, the sensitivity, specificity and κ were 67%, 99%, and 0.66, respectively. Conclusions: This study indicates that retrospectively obtained family histories are very accurate for breast cancer. For ovarian cancer, family histories are less precise and may need additional verificatio

Gene expression profiling of Leishmania (Leishmania) donovani: overcoming technical variation and exploiting biological variation

Gene expression profiling is increasingly used in the field of infectious diseases for characterization of host, pathogen and the nature of their interaction. The purpose of this study was to develop a robust, standardized method for comparative expression profiling and molecular characterization of Leishmania donovani clinical isolates. The limitations and possibilities associated with expression profiling in intracellular amastigotes and promastigotes were assessed through a series of comparative experiments in which technical and biological parameters were scrutinized. On a technical level, our results show that it is essential to use parasite harvesting procedures that involve minimal disturbance of the parasite's environment in order to ‘freeze' gene expression levels instantly; this is particularly a delicate task for intracellular amastigotes and for specific ‘sensory' genes. On the biological level, we demonstrate that gene expression levels fluctuate during in vitro development of both intracellular amastigotes and promastigotes. We chose to use expression-curves rather than single, specific, time-point measurements to capture this biological variation. Intracellular amastigote protocols need further refinement, but we describe a first generation tool for high-throughput comparative molecular characterization of patients' isolates, based on the changing expression profiles of promastigotes during in vitro differentiatio

Non-invasive assessment of peri-implant mucosal thickness: A cross-sectional study.

BACKGROUND This study aimed to evaluate the reliability and reproducibility of different non-invasive methods for the assessment of peri-implant mucosal thickness. METHODS Subjects with two adjacent dental implants in the central maxillary region were included in this study. Three different methods to assess facial mucosal thickness (FMT) were compared: digital file superimposition using Digital Imaging and Communication in Medicine (DICOM) and stereolithography (STL) files of the arch of interest (DICOM-STL), DICOM files alone, and non-ionizing ultrasound (US). Inter-rater reliability agreements between different assessment methods were analyzed using inter-class correlation coefficients (ICCs). RESULTS A total of 50 subjects with 100 bone-level implants constituted the study population. Assessment of FMT using STL and DICOM files demonstrated excellent inter-rater reliability agreement. Mean ICC values of 0.97 and 0.95 were observed in the DICOM-STL and DICOM groups, respectively. Comparison between the DICOM-STL and US revealed good agreement, with an ICC of 0.82 (95% CI: 0.74 to 0.88) and a mean difference of -0.13 ± 0.50 mm (-1.13 to 0.86). Comparison between DICOM files alone versus US showed good agreement, with an ICC of 0.81 (95% CI: 0.73 to 0.89) and a mean difference of -0.23 ± 0.46 mm (-1.12 to 0.67). Comparison between DICOM-STL and DICOM files revealed excellent agreement, with an ICC of 0.94 (95% CI: 0.91 to 0.96) and a mean difference of 0.1 ± 0.29 mm (LOA -0.47 to 0.46). CONCLUSIONS Quantification of peri-implant mucosal thickness via analysis of DICOM-STL files, DICOM files, or US assessment are comparably reliable and reproducible methods

Impact of a positive family history on diagnosis, management, and survival of breast cancer: different effects across socio-economic groups

Background: This study aims to investigate whether increased awareness of breast cancer, due to a positive family history (FH), reduces diagnostic, therapeutic, and survival differences between women of low versus high socio-economic status (SES). Methods: All breast cancer patients registered between 1990 and 2005 at the population-based Geneva Cancer Registry were included. With multivariate logistic and Cox regression analysis, we estimated the impact of SES and FH on method of detection, treatment, and mortality from breast cancer. Results: SES discrepancies in method of detection and suboptimal treatment, as seen among women without a FH, disappeared in the presence of a positive FH. SES differences in stage and survival remained regardless of the presence of a positive FH. Overall, positive FH was associated with better survival. This effect was the strongest in women of high SES (age-adjusted Hazard Ratio [HRageadj] 0.54 [0.3-1.0]) but less pronounced in women of middle (0.77 [0.6-1.0]), and absent in women of low SES (0.80 [0.5-1.2]). Conclusion: A positive FH of breast cancer may reduce SES differences in access to screening and optimal treatment. However, even with better access to early detection and optimal treatment, women of low SES have higher risks of death from their disease than those of high SE

Accuracy of five algorithms to diagnose gambiense human African trypanosomiasis.

Algorithms to diagnose gambiense human African trypanosomiasis (HAT, sleeping sickness) are often complex due to the unsatisfactory sensitivity and/or specificity of available tests, and typically include a screening (serological), confirmation (parasitological) and staging component. There is insufficient evidence on the relative accuracy of these algorithms. This paper presents estimates of the accuracy of five algorithms used by past Médecins Sans Frontières programmes in the Republic of Congo, Southern Sudan and Uganda