Dyspnea, like pain, can cause major suffering in intensive care unit (ICU) patients. Its evaluation relies on self-report; hence, the risk of being overlooked when verbal communication is impaired. ...Observation scales incorporating respiratory and behavioral signs (respiratory distress observation scales RDOS) can provide surrogates of dyspnea self-report in similar clinical contexts (palliative care).
The authors prospectively studied (single center, 16-bed ICU, large university hospital) 220 communicating ICU patients (derivation cohort, 120 patients; separate validation cohort, 100 patients). Dyspnea was assessed by dyspnea visual analog scale (D-VAS) and RDOS calculated from its eight components (heart rate, respiratory rate, nonpurposeful movements, neck muscle use during inspiration, abdominal paradox, end-expiratory grunting, nasal flaring, and facial expression of fear). An iterative principal component analysis and partial least square regression process aimed at identifying an optimized D-VAS correlate (intensive care RDOS IC-RDOS).
In the derivation cohort, RDOS significantly correlated with D-VAS (r = 0.43; 95% CI, 0.29 to 0.58). A five-item IC-RDOS (heart rate, neck muscle use during inspiration, abdominal paradox, facial expression of fear, and supplemental oxygen) significantly better correlated with D-VAS (r = 0.61; 95% CI, 0.50 to 0.72). The median area under the receiver operating curve of IC-RDOS to predict D-VAS was 0.83 (interquartile range, 0.81 to 0.84). An IC-RDOS of 2.4 predicted D-VAS of 4 or greater with equal sensitivity and specificity (72%); an IC-RDOS of 6.3 predicted D-VAS of 4 or greater with 100% specificity. Similar results were found in the validation cohort.
Combinations of observable signs correlate with dyspnea in communicating ICU patients. Future studies in noncommunicating patients will be needed to determine the responsiveness to therapeutic interventions and clinical usefulness.
Procalcitonin (PCT) has been proposed as a marker for malaria severity in adults, with a threshold of 10 ng/ml for severe falciparum disease. Whether PCT is useful in children is debated.
A ...retrospective case-control study was conducted to compare initial PCT levels in children with uncomplicated malaria and a control group, and between children with uncomplicated and severe malaria.
Results showed significantly higher PCT levels in malaria cases compared to the control group and in malaria severe cases compared to uncomplicated cases. A Receiving Operator Characteristic curve established a PCT threshold of 0.65 ng/ml with a negative predictive value of 98.8 % based on a prevalence of 10 %. Analyzing the pooled results of five studies suggested a threshold of 6.17 ng/ml for differentiating uncomplicated and severe malaria.
PCT might be a useful tool to help rule out malaria and predict potential disease severity in returning travelers.
•PCT discriminates between uncomplicated malaria and controls (threshold = 0.65 ng/ml).•PCT discriminates between severe and uncomplicated malaria (threshold = 6.17 ng/ml).•PCT might help predict an uncomplicated or a severe malaria case.
to BLAST analyses (https://blast.ncbi.nlm.nih.gov/Blast. cgi). The YFV Uganda 2016 strain envelope sequence was aligned with reference YFV genomes by using MAFFT through the EMBL-EBI server ...(www.ebi.ac.uk), and phylogenies were generated with BEAST 1.8.4 (9), as previously described (7). BLAST analyses determined that the highest percentage identity (95%) is shared between the Uganda 2016 strain and strains from South Sudan 2003 in the envelope region (the only region for which data from the Sudan strain are available) versus 83% with Angola 2016 strains from the same region. Furthermore, the Uganda 2016 sequences corresponding to the NS genes NS3 and NS5 have the highest percentage identities (94% and 95%, respectively) with a Uganda 1948 strain relative to 85% and 84% with the Angola 2016 strains in the same regions. Together these BLAST analyses indicate that the Uganda 2016 YFV is most similar to strains in the East African genotype. Phylogenetic analyses confirm the BLAST analyses and place the Uganda 2016 YFV in a well-supported clade along with these East African genotype strains, whereas the Angola 2016 strains group with an Angola 1971 YFV (Figure), indicating that the Uganda outbreak in 2016 was not seeded by the Angola outbreak. These findings reiterate the endemicity of YFV throughout the tropical regions of Africa because at least 2 concurrent yellow fever outbreaks of independent origins were identified in 2016. Our findings also highlight the importance of assessing the molecular epidemiology of the virus in outbreak investigations. These data improve our understanding of YFV epidemiology in Africa and support the previous studies of Mutebi and colleagues (2). In addition, removal of contaminating ribosomal RNA proved to be an effective method for unbiased enrichment of viral RNA in degraded samples to enhance sequencing sensitivity.
We evaluated the usefulness of an
quantitative PCR assay performed in bronchoalveolar lavage fluid (BAL) for the diagnosis and prognosis of both invasive and non-invasive aspergillosis.
This 4-year ...retrospective study involved 613 at-risk patients who had either hematological disorders or other immunosuppressive conditions, notably solid organ transplants. Thirty-five patients had proven/probable aspergillosis and thirteen had chronic non-invasive aspergillosis. We compared PCR, galactomannan index and mycological analysis of BAL.
For invasive aspergillosis (IA), PCR performed in BAL yielded 88.6% sensitivity and 95.5% specificity. Comparatively, galactomannan index and mycological examination yielded only 56.3 and 63.6% sensitivity and 97.6 and 94.5% specificity, respectively. Considering the 13 chronic aspergillosis cases, PCR, galactomannan index and mycological examination yielded 76.9, 15.4, and 84.6% sensitivity and 92.2, 94.9, and 93% specificity, respectively. Fungal load in BAL evaluated by PCR was able to discriminate between aspergillosis and contamination, but not between invasive and non-invasive forms. Finally, fungal load was predictive of 90-day mortality, with 23.1% mortality for patients with less than 500 copies/mL versus 68.4% for patients above that cut-off (
< 0.05).
Our results indicate that
PCR in BAL is of particular interest for both the diagnosis and the prognosis of IA. It is likewise an interesting tool for the diagnosis of non-invasive forms.
Adhesion to digestive mucosa is considered a crucial first step in the pathogenicity of invasive Candida infections. Candida glabrata disseminated infections predominantly start from the gut. A mouse ...model of disseminated infection starting from the gut was set up. Hematogenous dissemination was obtained after a low-protein diet followed by a regimen of cyclophosphamide-methotrexate and an oral inoculation of the yeasts via the drinking water. The liver was the first organ infected (day 7 post-infection), and lethality was 100% at day 21 post-infection. This new mouse model was used to compare the mortality rate and fungal burden in deep organs induced by 5 strains exhibiting different levels of adhesion to enterocyte Caco-2 cells, as determined in a test on 36 C. glabrata strains. In this model, no statistical difference of lethality was demonstrated between the strains, and fungal burden varied in kidneys and lungs but without correlation with the level of adhesion to enterocytes. Further studies using the model developed here allow analysis of the crossing of the digestive mucosa by yeasts, and help relate this to yet-poorly understood adhesion phenotypes.
Cysticercosis is a serious public health problem in Madagascar. The prevalence rate of active cysticercosis reached 21% in regions with a high level of livestock farming.
Taenia solium of ...African–American and Asian genotypes are both present on the island. The times of divergence of the 13 specimens studied suggests a very ancient diversification of
T. solium. These events are widely thought to be prior to the domestication of pigs, and seem to follow the expansion of
Homo in Asia. Multiple human migrations and the diversity of potential intermediate hosts may have led to a complex epidemiological situation on the island.
The coherent and coordinated strategy put in place since the beginning of the century to fight malaria has led to a significant reduction in the global burden of the disease. Of the various elements ...composing this strategy, it appears that vector control and, in the first place, the massive distribution of LLIN (long-lasting impregnated nets) have contributed significantly to this success. The idea, a priori trivial, of impregnating nets with insecticide to make them more effective, emerged in the late 1980s in Benin. Since then, thanks to the ongoing support of WHO and collaboration with industry, there has been a paradigm shift that puts LLIN at the forefront of malaria control. This chapter summarizes, in chronological order, the different steps that led to the use of LLIN, starting with simple mosquito nets. It provides a brief overview of the studies that have shown their effectiveness both from the entomological and the morbidity and mortality point of view. Finally, it presents the limitations and challenges that will need to be overcome if LLIN are to remain an effective tool in the fight against malaria.
Alphaviruses, including Chikungunya virus (CHIKV), produce a transient illness in humans, but severe forms leading to chronic incapacitating arthralgia/arthritis have been reported by mechanisms ...largely ill-characterized. The pathogenesis of CHIKV was addressed in a prospective cohort study of 49 hospitalized patients from Reunion Island subsequently categorized into two distinct groups at 12 mo postinfection. Comprehensive analyses of the clinical and immunological parameters throughout the disease course were analyzed in either the "recovered" or the "chronic" groups to identify prognostic markers of arthritis-like pathology after CHIKV disease. We found that the chronic group consisted mainly of more elderly patients (>60 y) and with much higher viral loads (up to 10(10) viruses per milliliter of blood) during the acute phase. Remarkably, a rapid innate immune antiviral response was demonstrated by robust dendritic/NK/CD4/CD8 cell activation and accompanied by a rather weak Th1/Th2 cytokine response in both groups. Interestingly, the antiviral immune response witnessed by high levels of IFN-alpha mRNA in PBMCs and circulating IL-12 persisted for months only in the chronic group. CHIKV (RNA and proteins) was found in perivascular synovial macrophages in one chronic patient 18 mo postinfection surrounded by infiltrating NK and T cells (CD4(++) but rare cytotoxic CD8). Fibroblast hyperplasia, strong angiogenesis, tissue lesions given the high levels of matrix metalloproteinase 2, and acute cell death high cleaved poly(ADP-ribose) polymerase staining were observed in the injured synovial tissue. These observed cellular and molecular events may contribute to chronic arthralgia/arthritis targeted by methotrexate used empirically for effective treatment but with immunosuppressive function in a context of viral persistence.
Background
In South-East Asia, Thailand is the country with the highest number of human autochthonous cases of leishmaniases mostly due to
Leishmania martiniquensis
. Their transmission remains ...unresolved to date even though sand flies are known vectors of leishmaniases. As such, we focused a study on the sand fly fauna of a cave in Thailand to explore the biodiversity of potential
Leishmania
vectors.
Main results
We carried out an inventory in Pha Tong cave. We caught and identified 570 Phlebotomine sand flies (452 females and 118 males) and identified 14 species belonging to the genera
Phlebotomus
,
Idiophlebotomus
,
Chinius
,
Sergentomyia
and
Grassomyia
. Among these 14 species, two could not be related to known sand fly species. Herein, we propose the description of two new sand fly species, previously unknown to science.
The first new species,
Phlebotomus shadenae
n. sp. is a sand fly of the subgenus
Anaphlebotomus
. It is morphologically close to
Ph
.
stantoni
, a species widely distributed throughout Southeast Asia. However, it differs by the length of the genital filaments in males or by the length of the ducts of the spermathecae in females as well as the high divergence of cytochrome b sequences. Additionally, we revised the systematics of the subgenus
Anaphlebotomus
and reinstated, by examination of its holotype, the validity of
Ph
.
maynei
, an Indian wrongly considered as a synonym of
Ph
.
stantoni
in the past.
The second new species,
Sergentomyia maiae
n. sp., differs from a species in the same group,
Se
.
barraudi
, by an original cibarial double row of vertical teeth as well as by molecular data.
Conclusions
We propose the description of two new sand fly species for Science with morphological and molecular evidence.
Ph
.
shadenae
n. sp. was also found to be distributed in the south of Thailand and in Laos. Future studies need to determine whether these two species can play a role as vectors of
Leishmania
parasites, Trypanosomatids or Phlebovirus. Most of the species caught in the present study are strictly cavernicolous except
Grassomyia
sp. and a few
Sergentomyia
.
Anopheles species identification is essential for an effective malaria vector control programme. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) has been ...developed to identify adult Anopheles species, using the legs or the cephalothorax. The protein repertoire from arthropods can vary according to compartment, but there is no general consensus regarding the anatomic part to be used.
To determine the body part of the Anopheles mosquitoes best suited for the identification of field specimens, a mass spectral library was generated with head, thorax with wings and legs of Anopheles gambiae, Anopheles arabiensis and Anopheles funestus obtained from reference centres. The MSL was evaluated using two independent panels of 52 and 40 An. gambiae field-collected in Mali and Guinea, respectively. Geographic variability was also tested using the panel from Mali and several databases containing added specimens from Mali and Senegal.
Using the head and a database without specimens from the same field collection, the proportion of interpretable and correct identifications was significantly higher than using the other body parts at a threshold value of 1.7 (p < 0.0001). The thorax of engorged specimens was negatively impacted by the blood meal after frozen storage. The addition of specimens from Mali into the database significantly improved the results of Mali panel (p < 0.0001), which became comparable between head and legs. With higher identification scores, the using of the head will allow to decrease the number of technical replicates of protein extract per specimen, which represents a significant improvement for routine use of MALDI-TOF MS.
The using of the head of Anopheles may improve the performance of MALDI-TOF MS. Region-specific mass spectrum databases will have to be produced. Further research is needed to improve the standardization in order to share online spectral databases.