Lifting dyspnoea invisibility: COVID-19 face masks, the experience of breathing discomfort, and improved lung health perception - a French nationwide survey.

QUESTION ADDRESSED: In contrast with pain, dyspnoea is not visible to the general public, who lack the corresponding experiential baggage. We tested the hypothesis that the generalised use of face masks to fight severe acute respiratory syndrome coronavirus 2 dissemination could change this and sensitise people to respiratory health. METHODS: General population polling (1012-person panel demographically representative of the adult French population, quota sampling method; 517 (51%) female). 860 (85%) answered "no" to "treated for a chronic respiratory disease" ("respiratory healthy"), and 152 answered "yes" ("respiratory disease"). 14% of respiratory healthy respondents reported having a close family member treated for a chronic respiratory disease (RH-family+ ). Respondents described mask-related attitudes, beliefs, inconveniencies, dyspnoea and changes in their respiratory health vision . RESULTS: Compliance with masks was high (94.7%). Dyspnoea ranked first among mask inconveniencies (respiratory disease 79.3%, respiratory healthy 67.3%; p=0.013). "Air hunger" was the main sensory dyspnoea descriptor. Mask-related dyspnoea was independently associated with belonging to RH-family+ (OR 1.85, 95% CI 1.16-2.98) and removing masks to improve breathing (OR 5.21, 95% CI 3.73-7.28). It was negatively associated with considering masks effective to protect others (OR 0.42, 95% CI 0.25-0.75). Half the respondents were more concerned with their respiratory health since wearing masks; 41% reported better understanding patients' experiences. ANSWER TO THE QUESTION: Wearing protective face masks leads to the mass discovery of breathing discomfort. It raises public awareness of what respiratory diseases involve and sensitivity to the importance of breathing. These data should be used as the fulcrum of respiratory health oriented communication actions.

Intravenous Artesunate for the Treatment of Severe Imported Malaria: Implementation, Efficacy, and Safety in 1391 Patients.

BACKGROUND: Intravenous artesunate is the World Health Organization-recommended first-line treatment for severe malaria worldwide, but it is still not fully licensed in Europe. Observational studies documenting its safety and efficacy in imported malaria are thus essential. METHODS: We prospectively collected clinical and epidemiological features of 1391 artesunate-treated patients among 110 participant centers during the first 7 years (2011-2017) of a national program implemented by the French Drug Agency. RESULTS: Artesunate became the most frequent treatment for severe malaria in France, rising from 9.9% in 2011 to 71.4% in 2017. Mortality was estimated at 4.1%. Treatment failure was recorded in 27 patients, but mutations in the Kelch-13 gene were not observed. Main reported adverse events (AEs) were anemia (136 cases), cardiac events (24, including 20 episodes of conduction disorders and/or arrhythmia), and liver enzyme elevation (23). Mortality and AEs were similar in the general population and in people with human immunodeficiency virus, who were overweight, or were pregnant, but the only pregnant woman treated in the first trimester experimented a hemorrhagic miscarriage. The incidence of post-artesunate-delayed hemolysis (PADH) was 42.8% when specifically assessed in a 98-patient subgroup, but was not associated with fatal outcomes or sequelae. PADH was twice as frequent in patients of European compared with African origin. CONCLUSIONS: Artesunate was rapidly deployed and displayed a robust clinical benefit in patients with severe imported malaria, despite a high frequency of mild to moderate PADH. Further explorations in the context of importation should assess outcomes during the first trimester of pregnancy and collect rare but potentially severe cardiac AEs.

New assessment of Anopheles vector species identification using MALDI-TOF MS.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Lung Ultrasound in Emergency and Critically Ill Patients: Number of Supervised Exams to Reach Basic Competence.

BACKGROUND: Lung ultrasound is increasingly used in critically ill patients as an alternative to bedside chest radiography, but the best training method remains uncertain. This study describes a training curriculum allowing trainees to acquire basic competence. METHODS: This multicenter, prospective, and educational study was conducted in 10 Intensive Care Units in Brazil, China, France and Uruguay. One hundred residents, respiratory therapists, and critical care physicians without expertise in transthoracic ultrasound (trainees) were trained by 18 experts. The main study objective was to determine the number of supervised exams required to get the basic competence, defined as the trainees' ability to adequately classify lung regions with normal aeration, interstitial-alveolar syndrome, and lung consolidation. An initial 2-h video lecture provided the rationale for image formation and described the ultrasound patterns commonly observed in critically ill and emergency patients. Each trainee performed 25 bedside ultrasound examinations supervised by an expert. The progression in competence was assessed every five supervised examinations. In a new patient, 12 pulmonary regions were independently classified by the trainee and the expert. RESULTS: Progression in competence was derived from the analysis of 7,330 lung regions in 2,562 critically ill and emergency patients. After 25 supervised examinations, 80% of lung regions were adequately classified by trainees. The ultrasound examination mean duration was 8 to 10 min in experts and decreased from 19 to 12 min in trainees (after 5 vs. 25 supervised examinations). The median training duration was 52 (42, 82) days. CONCLUSIONS: A training curriculum including 25 transthoracic ultrasound examinations supervised by an expert provides the basic skills for diagnosing normal lung aeration, interstitial-alveolar syndrome, and consolidation in emergency and critically ill patients.

Mortality from malaria in France, 2005 to 2014.

IntroductionMalaria is a notifiable disease in all European Union and European Economic Area countries except Belgium and France, where only autochthonous malaria is notifiable. Although morbidity caused by malaria has been assessed, little is known about mortality incidence.ObjectiveOur aim was to estimate the number of imported malaria-related deaths in hospital in metropolitan France.MethodsWe matched individual deaths reported between 1 January 2005 and 31 December 2014 to the French National Reference Centre for malaria (FNRCm) with malaria-related deaths from two other sources: the French National Registry on medical causes of death and the French national hospital discharge database. A capture-recapture method with log-linear modelling was used. Age, sex and place of death stratification were applied to remove heterogeneity.ResultsThe estimated malaria-related deaths in metropolitan France during the study period were 205 (95% confidence interval (CI): 191-219). The annual mean number of malaria-related deaths was estimated at 21 (95% CI: 19-22). The FNRCm malaria-related deaths surveillance had a 38% sensitivity (95% CI: 32-44). Among 161 in-hospital individual malaria-related deaths reported from three data sources, the sex ratio (male to female) was 2.6. Median age of the patients was 57 years, ranging from 1 to 89 years.ConclusionThe pertinent finding of this report is that malaria-related death records were significantly less complete [corrected] than case records. Therefore, data comparison of imported malaria morbidity and mortality between countries should imperatively be assessed using standard indicators weighted according to the completeness of health surveillance systems.

Stage-dependent fate of Plasmodium falciparum-infected red blood cells in the spleen and sickle-cell trait-related protection against malaria.

BACKGROUND: Sickle-cell trait (HbAS) reduces falciparum malaria risk and suppresses parasitaemia. Although several candidate mechanisms have been proposed, their epidemiological, clinical and experimental correlates have not been adequately explained. To explore the basis for generally lower parasitaemias and delayed malaria episodes in children with HbAS, it is hypothesized here that their spleen-dependent removal of ring-infected red blood cells (RBCs) is more efficient than in children with normal haemoglobin A (HbAA). METHODS: The mechanical splenic retention of Plasmodium falciparum-infected RBCs from subjects with HbAS or HbAA was investigated using two physiologically relevant methods: microsphiltration and ex vivo spleen perfusion. P. falciparum-infected RBCs obtained from in vitro cultures and from patients were used in either normoxic or hypoxic conditions. The effect of sickling in ring-infected HbAS RBCs was also investigated. RESULTS: When a laboratory-adapted parasite strain was analysed, ring-infected HbAA RBCs were retained in microsphilters at similar or greater levels than ring-infected HbAS RBCs, under normoxic (retention rate 62.5 vs 43.8 %, P < 0.01) and hypoxic (54.0 vs 38.0 %, P = 0.11) conditions. When parasitized RBCs from Malian children were analysed, retention of ring-infected HbAA and HbAS RBCs was similar when tested either directly ex vivo (32.1 vs 28.7 %, P = 0.52) or after one re-invasion in vitro (55.9 vs 43.7 %, P = 0.30). In hypoxia, sickling of uninfected and ring-infected HbAS RBCs (8.6 vs 5.7 %, P = 0.51), and retention of ring-infected HbAA and HbAS RBCs in microsphilters (72.5 vs 68.8 %, P = 0.38) and spleens (41.2 vs 30.4 %, P = 0.11), also did not differ. Retention of HbAS and HbAA RBCs infected with mature P. falciparum stages was greater than 95 %. CONCLUSIONS: Sickle-cell trait is not associated with higher retention or sickling of ring-infected RBCs in experimental systems reflecting the mechanical sensing of RBCs by the human spleen. As observed with HbAA RBCs, HbAS RBCs infected with mature parasites are completely retained. Because the cytoadherence of HbAS RBCs infected with mature parasites is impaired, the very efficient splenic retention of such non-adherent infected RBCs is expected to result in a slower rise of P. falciparum parasitaemia in sickle-cell trait carriers.

Diagnostic Accuracy of Respiratory Distress Observation Scales as Surrogates of Dyspnea Self-report in Intensive Care Unit Patients.

BACKGROUND: 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). METHODS: 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]). RESULTS: 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. CONCLUSIONS: 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.

Drying anti-malarial drugs in vitro tests to outsource SYBR green assays.

BACKGROUND: Measurement of anti-malarial drug efficacy and resistance relies mainly on in vivo clinical trials, in vitro/ex vivo assays and molecular markers detection. The existing in vitro/ex vivo assays, in particular those that are using non-radioactive devices, need to be standardized and adapted to field conditions. SYBR Green assay offers a rapid and cheap alternative to other in vitro assays, but it requires tools not commonly available in field laboratories. Here is described a modified SYBR green I protocol to perform the parasite growth test with blood samples in endemic areas, followed later by the SYBR green fluorescence assay performed at a specialized laboratory level. METHODS: In vitro susceptibility of Plasmodium falciparum clones HB3, 3D7, W2 and 7G8 to chloroquine (CQ), dihydroartemisinin (DHA), pyronaridine (PYD) and piperaquine (PPQ) was tested. Fresh isolates of P. falciparum from imported malaria cases were collected for ex vivo assays. The parasite suspension was added in 96-well plates predosed with anti-malarial drugs and incubated for 72 hours at 37°C, 5% CO2. SYBR green I protocol was modified to dry the plates after freeze-thawed process to mimic storage and shipping conditions. The plates were rehydrated with 200 µl of complete RPMI medium for fluorescence assay. RESULTS: There were no significant differences in IC50 values of CQ, DHA, PYD and PPQ, determined by the modified protocol, compared to standard protocol. Longer storage did not affect the IC50 values. CONCLUSION: The SYBR green I modified protocol produced reliable results and could be a suitable method for in vitro/ex vivo assays in field.

The risk of multiple sclerosis on the Orkney islands. A review of the search for distinctively Orcadian risks, with a hypothesis for further investigations.

The most extensive and meticulous epidemiological study yet to be published on the frequency of multiple sclerosis (MS) across the regions of Scotland has confirmed that the high incidence of MS on the Orcadian islands is unique and is most probably the highest in the world. Environmental and genetic studies of Orcadian MS have been carried out over many years but the results have been discouragingly inconclusive; no convincing explanation of the distinctively high Orcadian MS risks has come to light. However, studies of both prevalence and incidence of MS over a time line of approximately five decades, show that Orcadian MS has steadily increased to significantly exceed the neighbouring genetically related populations including North Eastern Scotland and the Shetland islands. Over this period the islands have progressively expanded occupations related to agriculture and have simultaneously acquired the highest concentration of cattle in Europe. Coinciding high and increasing Orcadian MS risk with increasing agricultural activities including bovine density and dairying, points towards a potential but unexpected causal risk. Raised incidence of MS with farming and in particular with dairy farming have been documented in Australia, Denmark, and more recently in Norway, further pointing to a possible MS risk associated with agricultural activities. A clue to the cause of this curious association has unexpectedly emerged from laboratory studies. Using very rarely available tissues from patients coming to autopsy during an MS attack, a toxin known as beta-haemolysin (sphingomyelinase), which is produced by the bacterium Staphylococcus aureus, has been identified in the affected tissues. Staph aureus is a common inhabitant of the mucosal linings of the human nasal sinuses and sinus mucosal inflammations have been shown to be closely associated with attacks of MS and optic neuritis. Irrespective of origin, human or animal, all strains of Staph aureus carry the beta haemolysin gene. However, the toxin is only sporadically expressed by the strains most commonly isolated from human carriers. Strains carried by bovines nearly always express toxin. Has the increasing high risk of MS in Orcadians been promoted by the nasal transmission and subsequent establishment of the high secreting bovine genotypes of Staph aureus in the Orcadian population? To demonstrate that bovine associated strains of Staph aureus are carried more frequently in the Orcadian population (or even specifically in Orcadian MS cases), would not of itself necessarily explain the high prevalence of Orcadian MS. It would however clearly justify an in-depth exploration of the nasal bacterial microbiome of MS cases. This should include the incidence of beta-toxin secreting Staph aureus genotypes. If MS cases are shown to have a distinctive nasal bacterial microbiome, including beta-toxin secretors, this finding would open up an almost entirely new range of investigations and approaches to the understanding of the pathogenesis of MS.

Might procalcitonin help predict imported falciparum malaria in children?

BACKGROUND: 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. PATIENTS & METHODS: 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: 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. CONCLUSION: PCT might be a useful tool to help rule out malaria and predict potential disease severity in returning travelers.

Phlebotomine sand flies (Diptera, Psychodidae) from Pha Tong cave, Northern Thailand with a description of two new species and taxonomical thoughts about Phlebotomus stantoni.

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.

Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response.

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.

'Involve me and I learn': an experiential teaching approach to improve dyspnea awareness in medical residents.

BACKGROUND: Dyspnea is a frightening and debilitating experience. It attracts less attention than pain ('dyspnea invisibility'), possibly because of its non-universal nature. We tested the impact of self-induced experimental dyspnea on medical residents. MATERIALS AND METHODS: During a teaching session following the principles of experiential learning, emergency medicine residents were taught about dyspnea theoretically, observed experimental dyspnea in their teacher, and personally experienced self-induced dyspnea. The corresponding psychophysiological reactions were described. Immediate and 1-year evaluations were conducted to assess course satisfaction (overall 0-20 grade) and the effect on the understanding of what dyspnea represents for patients. RESULTS: Overall, 55 emergency medicine residents participated in the study (26 men, median age 26 years). They were moderately satisfied with previous dyspnea teaching (6 [5-7] on a 0-10 numerical rating scale [NRS]) and expressed a desire for an improvement in the teaching (8 [7-9]). Immediately after the course they reported improved understanding of patients' experience (7 [6-8]), which persisted at 1 year (8 [7-9], 28 respondents). Overall course grade was 17/20 [15-18], and there were significant correlations with experimental dyspnea ratings (intensity: r = 0.318 [0.001-0.576], p = 0.043; unpleasantness: r = 0.492 [0.208-0.699], p = 0.001). In multivariate analysis, the only factor independently associated with the overall course grade was 'experiential understanding' (the experimental dyspnea-related improvement in the understanding of dyspneic patients' experience). A separate similar experiment conducted in 50 respiratory medicine residents yielded identical results. CONCLUSIONS: This study suggests that, in advanced medical residents, the personal discovery of dyspnea can have a positive impact on the understanding of what dyspnea represents for patients. This could help fight dyspnea invisibility.

The pig tapeworm Taenia solium, the cause of cysticercosis: Biogeographic (temporal and spacial) origins in Madagascar.

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.

Determination of anti-leishmanial drugs efficacy against Leishmania martiniquensis using a colorimetric assay.

Autochthonous leishmaniasis caused by Leishmania martiniquensis cases in Thailand have dramatically increased in the recent years. L. martiniquensis infection primarily occurs in immunocompromised patients, especially AIDS patients. In Thailand, amphotericin B is the only drug available for leishmaniasis treatment, and some patients relapse after amphotericin B therapy. Moreover, the efficacy of anti-leishmanial drugs against L. martiniquensis has not been evaluated to date. In this study, we determined the efficacy of various anti-leishmanial drugs against the promastigote and intracellular amastigote stages of L. martiniquensis using a colorimetric assay. Two strains (CU1 and CU1R1) were isolated from leishmaniasis HIV co-infected patient from Songkhla province, southern Thailand. The CU1 strain was isolated from the patient in 2011, and CU1R1 was isolated from the same patient in 2013, when he was diagnosed as relapse leishmaniasis. The third strain (LSCM1) used in this study has been isolated from immunocompetent patient from Lamphun province, northern Thailand. All strains were identified as L. martiniquensis by sequencing of ribosomal RNA ITS-1 and large subunit of RNA polymerase II gene. Bioassays have been conducted both with promastigote and intracellular amastigote stages of the parasite. All L. martiniquensis strains have been tested against amphotericin B, miltefosine and pentamidine to determine the efficacy of the drugs against the parasite by using a PrestoBlue. The efficacy of miltefosine and pentamidine exhibit no significant difference between each stage of L. martiniquensis among all strains. Surprisingly, the promastigote and intracellular amastigote of the CU1R1 isolate, which was isolated from a relapsed patient after amphotericin B treatment, exhibited a two-fold increased inhibitory concentration (IC50) against amphotericin B compared with other strains, and the difference was statistically significant (p < 0.05). Moreover, intracellular amastigotes isolated from CU1R1 exhibited slightly increased susceptibility to amphotericin B compared with the promastigote (p < 0.05). The result of this experiment is a scientific evident to support that in case of relapsed leishmaniasis caused by L. martiniquensis, increasing dosage of amphotericin B is essential. Moreover, this study also determined efficacy of other anti-leishmanial drugs for treatment the leishmaniasis in Thailand in case of these drugs are available in the country and the clinicians should have alternative drugs for treatment leishmaniasis in Thailand apart from amphotericin B.

Intraoperative pulmonary hyperdistention estimated by transthoracic lung ultrasound: A pilot study.

INTRODUCTION: Transthoracic lung ultrasound can assess atelectasis reversal and is considered as unable to detect associated hyperdistention. In this study, we describe an ultrasound pattern highly suggestive of pulmonary hyperdistention. METHODS: Eighteen patients with normal lungs undergoing lower abdominal surgery were studied. Electrical impedance tomography was calibrated, followed by anaesthetic induction, intubation and mechanical ventilation. To reverse posterior atelectasis, a recruitment manoeuvre was performed. Positive-end expiratory pressure (PEEP) titration was then obtained during a descending trial - 20, 18, 16, 14, 12, 10, 8, 6 and 4cmH2O. Ultrasound and electrical impedance tomography data were collected at each PEEP level and interpreted by two independent observers. Spearman correlation test and receiving operating characteristic curve were used to compare lung ultrasound and electrical impedance tomography data. RESULTS: The number of horizontal A lines increased linearly with PEEP: from 3 (0, 5) at PEEP 4cmH2O to 10 (8, 13) at PEEP 20cmH2O. The increase number of A lines was associated with a parallel and significant decrease in intercostal space thickness (p=0.001). The lung ultrasound threshold for detecting pulmonary hyperdistention was defined as the number of A lines counted at the PEEP preceding the PEEP providing the best respiratory compliance. Six A lines was the median threshold for detecting pulmonary hyperdistention. The area under the receiving operating characteristic curve was 0.947. CONCLUSIONS: Intraoperative transthoracic lung ultrasound can detect lung hyperdistention during a PEEP descending trial. Six or more A lines detected in normally aerated regions can be considered as indicating lung hyperdistention. TRIAL REGISTRATION: NCT02314845 Registered on ClinicalTrials.gov.

Insecticide-Treated Mosquito Nets.

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.