Background. The number of human deaths due to rabies is currently underestimated to be 55,000 deaths per year. Biological diagnostic methods for confirmation of rabies remain limited, because testing ...on postmortem cerebral samples is the reference method, and in many countries, sampling brain tissue is rarely practiced. There is a need for a reliable method based on a simple collection of nonneural specimens. Methods. A new reverse-transcription, heminested polymerase chain reaction (RT-hnPCR) protocol was standardized at 3 participating centers in Cambodia, Madagascar, and France. Fifty-one patients from Cambodia, Madagascar, Senegal, and France were prospectively enrolled in the study; 43 (84%) were ultimately confirmed as having rabies. A total of 425 samples were collected from these patients during hospitalization. We studied the accuracy of the diagnosis by comparing the results obtained with use of biological fluid specimens (saliva and urine) and skin biopsy specimens with the results obtained with use of the standard rabies diagnostic procedure performed with a postmortem brain biopsy specimen. Results. The data obtained indicate a high specificity (100%) of RT-hnPCR and a higher sensitivity (⩾98%) when the RT-hnPCR was performed with skin biopsy specimens than when the test was performed with fluid specimens, irrespective of the time of collection (i.e., 1 day after the onset of symptoms or just after death). Also, a sensitivity of 100% was obtained with the saliva sample when we analyzed at least 3 successive samples per patient. Conclusions. Skin biopsy specimens should be systematically collected in cases of encephalitis of unknown origin. These samples should be tested by RT-hnPCR immediately to confirm rabies; if the technique is not readily available locally, the samples should be tested retrospectively for epidemiological purposes.
Cholera is an acute diarrheal illness caused by Vibrio cholerae and occurs as widespread epidemics in Africa. In 2005, there were 31,719 cholera cases, with 458 deaths in the Republic of Senegal. We ...retrospectively investigated the climate origin of the devastating floods in mid-August 2005, in the Dakar Region of Senegal and the subsequent outbreak of cholera along with the pattern of cholera outbreaks in three other regions of that country. We compared rainfall patterns between 2002 and 2005 and the relationship between the sea surface temperature (SST) gradient in the tropical Atlantic Ocean and precipitation over Senegal for 2005. Results showed a specific pattern of rainfall throughout the Dakar region during August, 2005, and the associated rainfall anomaly coincided with an exacerbation of the cholera epidemic. Comparison of rainfall and epidemiological patterns revealed that the temporal dynamics of precipitation, which was abrupt and heavy, was presumably the determining factor. Analysis of the SST gradient showed that the Atlantic Ocean SST variability in 2005 differed from that of 2002 to 2004, a result of a prominent Atlantic meridional mode. The influence of this intense precipitation on cholera transmission over a densely populated and crowded region was detectable for both Dakar and Thiès, Senegal. Thus, high resolution rainfall forecasts at subseasonal time scales should provide a way forward for an early warning system in Africa for cholera and, thereby, trigger epidemic preparedness. Clearly, attention must be paid to both natural and human induced environmental factors to devise appropriate action to prevent cholera and other waterborne disease epidemics in the region.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Introduction
Hypertension results in more deaths than any other risk factor and has been on the rise in Sub-Saharan Africa over the past few decades. Generic drugs have helped improve ...accessibility and affordability of antihypertensive therapy in developing countries. However, assessment of quality standards of these products is important.
Purpose
We performed a quality assessment of five commonly used antihypertensive generic drugs in ten Sub-Saharan African countries and studied the impact of price on quality.
Methods
Drug samples were prospectively collected using standardized methods between 2012 and 2014. We developed a validated reversed-phase liquid chromatography with tandem mass spectrometry method to accurately quantify the active ingredient in a certified public laboratory. Quality was defined based on the percentage ratio of measured to expected dosage of active ingredient.
Results
A total of 1185 samples were assessed, of which 70.0% were generic (n=830). Among the generic drugs, the percentage of poor quality drugs was 24.3% (n=202/830). The percentage ratio of measured to expected dosage of active ingredient ranged from 49.2% to 111.3%; the majority (81.7%) of the poor quality samples had insufficient quantity of the active ingredient. Moreover, poor quality was not associated with purchase price of the drug.
Conclusion
In this study from ten Sub-Saharan African countries, nearly one-quarter of the available generic antihypertensive drugs were found to be of poor quality. Concerted measures to improve the quality of antihypertensive drugs could lead to major improvements in hypertension control with attendant reduction of its deleterious consequences in low and middle income countries.
Figure 1. Percentage of poor quality in generic antihypertensive drugs according to the country of purchase.
Acknowledgement/Funding
Grant AAP-2014-042, ANSM (Agence Nationale Sécurité du Médicament
To determine the predictive value of chloroquine (CQ) resistance markers in Senegal, Plasmodium falciparum DNA polymorphisms in pfmdr1and pfcrt were examined in relation to clinical outcome. Despite ...CQ treatment, 17% of patients had parasitemia after 28 days. Examination of molecular markers of CQ resistance revealed that 64% of all isolates had the T76 resistant allele at the pfcrt locus, while 30% carried the Y86 resistant allele at the pfmdr1 locus. The pfcrt T76 allele was present not only in all in vivo resistant isolates, 89% of in vitro resistant isolates, but also in 35% of in vitro sensitive isolates. The pfmdr1 N86Y polymorphism did not correlate with in vitro or in vivo CQ resistance. Our data suggest that the pfcrt T76 allele alone is required but not a sufficient predictor for in vivo CQ resistance.
•Atrophy and White Matter Hyperintensities were prevalent in Senegalese people aged ≥50.•No clear HIV impact was observed.•The role of comorbidities, such as hypertension, was highlighted.•Brain MRI ...studies are encouraged in this population living in West Africa.
To cross-sectionally describe brain alterations in PLHIV aged above 50 years old, receiving antiretroviral treatment (ART) and living in Senegal compared to HIV-negative subjects.
Twenty PLHIV and 26 HIV-negative subjects with comparable socio-demographic and clinical characteristics underwent an MRI exam (3D-T1 and FLAIR sequences). Global atrophy and White Matter Hyperintensities (WMH) were evaluated. After assessing the feasibility and acceptability of MRI scans in this population, we described atrophy and WHM prevalence and associated factors using logistic regressions.
Overall, 43.5% of the study sample were aged ≥60 years, 58.7% were women, and 28.3% had hypertension. The overall prevalence of atrophy and WMH was 19.6% 95% CI: 8.1–31.1 and 30.4% 95% CI: 17.1–43.7. HIV status had no significant effect on atrophy or WMH. Unemployment and hypertension were significantly associated with atrophy, whereas women were less likely to present atrophy. Aged ≥60 years was the only factor associated with WMH.
A high prevalence of atrophy and WMH was observed in West African adults aged over 50 years without a clear HIV impact. As brain MRI studies are critical to better understand cognitive and emotional outcomes, we encourage those studies in older PLHIV in West Africa.
The photo-induced fluorescence method is often applied to determine non-native fluorescent compounds. It typically uses UV irradiation from a high pressure mercury vapor discharge lamp to create ...photo-induced fluorescent compounds, which are then quantified by fluorescence spectroscopy. However, these mercury lamps require a high-voltage power supply and may accidentally induce electric shocks and the release of mercury vapors. As an alternative, we have evaluated in this technical note new UV-C germicidal lamps. These lamps exhibit a higher power at 254 nm and allowed us to obtain a far greater amount of photo-induced compounds in a shorter time. For the first time, this new irradiation system has been applied for the determination of pesticides in water and has shown a significant increase in the method sensitivity. These good results allowed us to conclude that the new UV-C lamps are a relevant alternative to high pressure mercury vapor discharge lamps for use with photo induced fluorescent methods.
This paper describes prototypes of an on-site early warning water quality monitoring system (EWWQMS) for pesticide quantification in natural waters by fluorescence and absorbance. As many pesticides ...are not naturally fluorescent, this EWWQMS uses UV irradiation to transform these compounds into highly fluorescent photoproducts and obtain sufficient sensitivity. To obtain a better specificity, the system uses four UV LEDs at different wavelengths to excite the fluorescent photoproducts. For pesticides that are not sensitive to photoconversion, the EWWQMS prototypes also use UV absorption for their quantification, thus offering a wider application range. A first system uses a diode array spectrometer for detection. A second system uses a higher resolution spectrometer and an intensified CCD camera detection to increase sensitivity. Analytical applications were conducted for the determination of fipronil, acetamipride, cyprodinil, trifluraline and pendimethaline in water using both the EWWQMS prototypes. The analytical performances of these new systems are good compared with other photo-induced fluorescence methods already published. Limits of detection without pre-concentration are in the range of 0.2 to 3 ng mL
−1
and the recovery values range from 95 to 108%. These results show that the EWWQMS prototypes can be used as an alert system to protect industrial plants from pesticide contaminations that exceed the capabilities of their cleaning processes.
The discovery of a new FeII oxalate framework of composition K2Fe(C2O4)2(H2O)2·0.18H2O is reported. Its crystal structure was solved by means of single crystal and powder X‐ray diffraction. The new ...organic–inorganic hybrid compound crystallizes in the orthorhombic space group Pca21 with unit‐cell parameters: a = 12.0351 (4) Å, b = 15.1265 (5) Å, c = 10.5562 (4) Å. This crystal structure, containing eight chemical formula, consists of a succession of FeO4(H2O)2 octahedra and K+ cations growing along b direction. Magnetization measurements indicate that the title compound is paramagnetic over the investigated temperature range (2–300 K). Both magnetization and 57Fe Mössbauer data indicate that Fe2+ is in a high‐spin state.
The crystal structure of a new FeII‐based metal organic framework of composition K2Fe(C2O4)2(H2O)2·0.18H2O is resolved using single crystal and powder X‐ray diffraction.
Fusion oncogenes are prevalent in several pediatric cancers, yet little is known about the specific associations between age and phenotype. We observed that fusion oncogenes, such as
, are associated ...with acute megakaryoblastic or other myeloid leukemia subtypes in an age-dependent manner. Analysis of a novel inducible transgenic mouse model showed that
expression in fetal hematopoietic stem cells induced rapid megakaryoblastic leukemia whereas expression in adult bone marrow hematopoietic stem cells resulted in a shift toward myeloid transformation with a strikingly delayed
leukemogenic potential. Chromatin accessibility and single-cell transcriptome analyses indicate ontogeny-dependent intrinsic and
-induced differences in the activities of key transcription factors, including ERG, SPI1, GATA1, and CEBPA. Importantly, switching off the fusion oncogene restored terminal differentiation of the leukemic blasts. Together, these data show that aggressiveness and phenotypes in pediatric acute myeloid leukemia result from an ontogeny-related differential susceptibility to transformation by fusion oncogenes. SIGNIFICANCE: This work demonstrates that the clinical phenotype of pediatric acute myeloid leukemia is determined by ontogeny-dependent susceptibility for transformation by oncogenic fusion genes. The phenotype is maintained by potentially reversible alteration of key transcription factors, indicating that targeting of the fusions may overcome the differentiation blockage and revert the leukemic state.
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