Prevalence of Chikungunya,Dengue and Zika viruses in blood donors: a systematic literature review and meta-analysis

BackgroundBlood transfusion centres should understand the epidemiology of emerging diseases that are transmissible through the transfusion of blood components. The risk of transmission of arboviruses through this route has become apparent in recent years. The aim of our study is to summarise the reported prevalence (viraemic rate, seroprevalence and/or antigen detection) of Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) viruses in blood donors according to screening test used and world region.Materials and methodsWe conducted a systematic literature review and meta-analysis having searched for information in the main bibliographic databases (MEDLINE, Embase, and Scopus). The prevalence for each of the viruses was calculated according to the screening test used and geographic location.ResultsWe included 18 records on CHIKV, 71 on DENV, and 27 on ZIKV. The highest prevalences of RNA for CHIKV were 1.9% in Puerto Rico (2014), 1.0% in Thailand (2009), and 1.0% in French Polynesia (2014–15). The highest prevalences of RNA for DENV were 5.5% in Saudi Arabia (2015–16), 2.3% in Madeira, Portugal (2012–13), and 0.6% in Brazil (2012). The highest prevalences of RNA for ZIKV were 2.8% in French Polynesia (2013–14), 2.7% in Brazil (2015–16), and 1.8% in Martinique (2016). Overall seroprevalence, as assessed by IgG antibodies, was 21.6% for CHIKV, 24.0% for DENV, and 5.1% for ZIKV.DiscussionOur study shows a high proportion of donors who are viraemic and asymptomatic, especially during outbreaks, with prevalences surpassing 5% for DENV, 1% for CHIKV, and 2% for ZIKV. These data confirm a clear threat to blood transfusion safety. The elevated seroprevalence for these three arboviruses is also indicative of their wide circulation in populations, correlating with an increased risk of infected but asymptomatic donors. Health centres and institutions must address this threat, especially in tropical regions where the biggest outbreaks occur.     

Everything that is not given is lost

A small health center is located in Velingara,Senegal.It is approximately 7 o'clock in the morning.In the old,dusty room that constitutes the operating room,a s...     

Phase I/II study of gefitinib and capecitabine in patients with colorectal cancer

Objective The objectives of this phase I/II study were to determine the maximum tolerated dose (MTD), characterise the principal toxicities in the phase I part and assess the efficacy in the phase II part of gefitinib, an oral selective inhibitor of the epidermal growth factor receptor, in combination with capecitabine in patients with advanced colorectal cancer (CRC). Methods and patients Patients with advanced CRC were treated with gefitinib administered daily for 21 days and capecitabine administered twice daily for 14 days of a 21-day cycle. The dose levels of gefitinib (mg) and capecitabine (mg/m² bid) assessed were 250/1000 and 250/ 1250. An expanded cohort was enrolled at the MTD to better characterise toxicity and efficacy. A total of 32 previously treated patients were accrued. In the phase I part 10 subjects were treated, with one dose-limiting toxicity. Overall 26 patients were treated at the MTD of the combination, which was gefitinib 250 mg/day and capecitabine 1250 mg/m² twice daily. Results The most frequent treatment-related adverse events included asthenia, diarrhoea, nausea, rash and anorexia. The incidence profile was very similar in phases I and II. No objective responses were documented but 53% of the patients achieved stable disease as best response to therapy. Conclusions Capecitabine 1250 mg/m² twice daily 14 of 21 days and gefitinib at 250 mg/day can be safely administered in combination. The combination is relatively well tolerated. There were no objective responses, although an interesting stabilisation rate was documented, in previously treated advanced CRC patients.     

The opposing effects of the flavonoids isoquercitrin and sissotrin, isolated from Pterospartum tridentatum, on oral glucose tolerance in rats

The effect of an aqueous extract of Pterospartum tridentatum on the blood glucose levels of normal Wistar rats was investigated in a situation of oral glucose challenge. The extract at 300 mg/kg showed an antihyperglycaemic effect in the first 30 min after glucose challenge but then the blood glucose levels rose above those of the control group, indicating the presence of compounds with different effects on glucose tolerance. Nine compounds of isoflavone and flavonol skeletons were identified in the extract by HPLC-ESI-MS(n), four of them being identified for the first time in this species. The isoflavone sissotrin and the flavonol derivative, isoquercitrin, were selected for the oral glucose tolerance test. Isoquercitrin (100 mg/kg) showed time-dependent antihyperglycaemic activity by delaying the post-oral glucose load glycaemic peak at 30 min, as did the sodium-dependent glucose transporter inhibitor phloridzin (100 mg/kg). In contrast, sissotrin (100 mg/kg) showed an opposite effect, impairing glucose tolerance. In conclusion, these preliminary results indicate that the effect of the extract on blood glucose may be either antihyperglycaemic or hyperglycaemic. Additionally, as far as is known, these are the first in vivo results on the acute antihyperglycaemic potential of isoquercitrin.     

Pronóstico perinatal y materno de la gestación múltiple en función del protocolo intraparto

Objectives

To evaluate maternal and fetal outcomes of multiple pregnancy according to route of delivery.

Material and methods

We performed a retrospective study of all twin deliveries in the previous 5 years and evaluated the route of delivery, especially in the final year. The information was recorded with Microsoft EXCEL and was analyzed with the statistical program SPSS 12.0 for Windows.

Results

The mean gestational age was 35.3 weeks. Route of delivery was through cesarean section in 59.8%. The mean interval between twins was 7.82 minutes when the first twin was delivered vaginally. Neonatal morbidity was found in 49%, and was higher in the second twin and in preterm deliveries.

Conclusions

Multiple pregnancies are associated with a large number of maternal and perinatal complications, as well as with a greater number of cesarean sections. Consequently, correct intrapartum management is required to reduce neonatal morbility as far as possible.     

The predictive value of soluble major histocompatibility complex class I chain-related molecule A (MICA) levels on heart allograft rejection

BACKGROUND: Recently the presence of a soluble form of major histocompatibility complex class I chain-related molecule A (sMICA) has been detected in the sera of patients with tumors. Shedding of sMICA by tumor cells downregulates NKG2D-mediated antitumor immunity. The aim of this investigation was to study the possible involvement of sMICA in the allograft acceptance after heart transplantation (HTX). METHODS: We monitored the levels of sMICA by specific enzyme-linked immunosorbent assay (ELISA) in a total of 146 serum samples obtained from 34 heart transplantation patients followed up during the first year post-HTX. RESULTS: The persistence of sMICA expression was correlated with the clinical evolution of these patients. sMICA was detected in the serum of 21 of 34 patients (61.70%) between 15 and 20 days after implantation and was practically absent in pretransplant serum samples. Twenty of these 21 patients (95.24%) with sMICA did not experience episodes of severe rejection during this period (P = 0.0001), whereas sMICA was practically absent in patients with manifestations of severe acute rejection. The longitudinal study of these patients revealed that the presence of sMICA was consistently maintained in 75% of the patients with good graft status during the period of observation. CONCLUSION: This has led us to believe that the presence of levels of sMICA during the first year post-HTX may contribute to allograft acceptance. Additionally, functional studies indicate that sMICA downregulates NKG2D surface expression, which may lead to a functional impairment of cell-mediated cytolysis. These data suggest a significant correlation between the presence of sMICA and a lower incidence of rejection.     

High intrapatient variability of tacrolimus exposure associated with poorer outcomes in liver transplantation

Tacrolimus (TAC) is a dose‐dependent immunosuppressor with considerable intrapatient variability (IPV) in its pharmacokinetics. The aim of this work is to ascertain the association between TAC IPV at 6 months after liver transplantation (LT) and patient outcome. This single‐center cohort study retrospectively analyzed adult patients who underwent transplantation from 2015 to 2019 who survived the first 6 months with a functioning graft. The primary end point was the patient’s probability of death and the secondary outcome was the loss of renal function between month 6 and the last follow‐up. TAC IPV was estimated by calculating the coefficient of variation (CV) of the dose‐corrected concentration (C₀/D) between the third and sixth months post‐LT. Of the 140 patients who underwent LT included in the study, the low‐variability group (C₀/D CV < 27%) comprised 105 patients and the high‐variability group (C₀/D CV ≥ 27%) 35 patients. One‐, 3‐, and 5‐year patient survival rates were 100%, 82%, and 72% in the high‐variability group versus 100%, 97%, and 93% in the low‐variability group, respectively (p = 0.005). Moreover, significant impaired renal function was observed in the high‐variability group at 1 year (69 ± 16 ml/min/1.73 m² vs. 78 ± 16 ml/min/1.73 m², p = 0.004) and at 2 years post‐LT (69 ± 17 ml/min/1.73 m² vs. 77 ± 15 ml/min/1.73 m², p = 0.03). High C₀/D CV 3–6 months remained independently associated with worse survival (hazard ratio = 3.57, 95% CI = 1.32–9.67, p = 0.012) and loss of renal function (odds ratio = 3.47, 95% CI = 1.30–9.20, p = 0.01). Therefore, high IPV between the third and sixth months appears to be an early and independent predictor of patients with poorer liver transplant outcomes.

Abbreviations

BPAR

Biopsy proven acute rejection

BMI

Body mass index

CKD‐EPI

chronic kidney disease epidemiology collaboration

CV

coefficient of variation

C₀/D

dose‐corrected concentration

CMV

cytomegalovirus

eGFR

estimated glomerular filtration rate

HR

hazard ratio

HCC

hepatocellular carcinoma

ICU

intensive care unit

IPV

intrapatient variability

i.v.

intravenously

LC–MS/MS

liquid chromatography‐ tandem mass spectrometry

LT

liver transplantation

MELD

model for end‐stage liver disease

MMF

mycophenolate mofetil

NASH

Non‐Alcoholic Steatohepatitis

OR

odds ratio

PCR

polymerase chain reaction

SD

Standard Deviation

TAC

tacrolimus

3–6 M

three–six months

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

There is high intrapatient variability of tacrolimus and its correlation with liver transplantation (LT) outcomes.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Could the intrapatient variability of tacrolimus between months 3 and 6 post‐LT be a potential prognostic tool for poor outcomes?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Those patients with dose‐corrected concentration coefficient of variation greater than or equal to 27% between months 3 and 6 post‐LT have worst overall survival and impaired renal function.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

If we promptly identify those patients, a closer therapeutic drug monitoring program should be imperative with the possibility to make therapeutic interventions to improve outcomes.     

Avoidant/restrictive food intake disorder symptoms in children: Associations with child and family variables

This study sought to determine the frequency of possible cases of avoidant/restrictive food intake disorder (ARFID) in a Portuguese sample of school-aged children and to assess the associations with child’s internalizing problems, BMI z-score and body dissatisfaction, and parents’ eating habits, attitudes and practices. We assessed 330 children through child’s and parents’measures. Fifty-one (15.5%) children were possible cases of ARFID based on their symptom’s presentation. There were no association between sex and possible cases of ARFID, and no significant differences between possible cases of ARFID and nonpossible cases of ARFID regarding age. Lower BMI z-score and anxiety/depression were associated with possible cases of ARFID.     

Efficacy of a spatial repellent for control of Aedes-borne virus transmission: A cluster-randomized trial in Iquitos,Peru

Over half the world’s population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABVs by releasing active ingredients into the air that disrupt mosquito–human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate, and parity status through mixed-effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34.1% (one-sided 95% CI lower limit, 6.9%; one-sided P value = 0.0236, z = 1.98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28.6 (95% CI 24.1%, ∞); z = −9.11) and 12.4% (95% CI 4.2%, ∞); z = −2.43), respectively. Our trial provides conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

Aedes-borne viral diseases (ABVDs) [e.g., dengue (DENV), chikungunya, Zika (ZIKV), and yellow fever] are devastating, expanding global public health threats that disproportionally affect low- and middle-income countries. DENV, one of the most rapidly increasing vector-borne infectious diseases, results in ∼400 million infections each year (1, 2), with 4 billion people at risk for infection annually (3). Currently, the primary means for ABVD prevention is controlling the primary mosquito vector, Aedes aegypti. Existing vector control interventions, however, have failed to prevent ABV transmission and epidemics (4–6).There is an urgent need to develop evidence-based guidance for the use of new and existing ABV vector control tools. The evidence base for vector control against ABVs is weak, despite considerable government investments in World Health Organization (WHO)-recommended control of larval habitats (larviciding, container removal) and ultra-low-volume insecticide spraying (4, 5, 7–9). These strategies continue to be implemented despite the lack of rigorously generated data from controlled clinical trials demonstrating they reduce ABV infection or disease (6). The only ABV intervention with a proven epidemiological impact in a cluster-randomized control trial (cRCT) assessed community mobilization to reduce mosquito larval habitats (10). A recent test-negative trial with Wolbachia-infected mosquitoes reported a significant reduction of DENV illness in Indonesia (11).Spatial repellents (SRs) are devices that contain volatile active ingredients that disperse in air. The active ingredients can repel mosquitoes from entering a treated space, inhibit attraction to human host cues, or disrupt mosquito biting and blood-feeding behavior and, thus, interfere with mosquito–human contact (12–14). Any of these outcomes reduce the probability of pathogen transmission. Pyrethroid-based SRs have shown efficacy in reducing malaria infections in China (15) and Indonesia (16). There have, however, been no clinical trials evaluating the protective efficacy (PE) of SRs against ABV infection or disease.To generate evidence for public health consideration, we conducted a double-blinded, parallel cRCT to demonstrate and quantify the PE of a transfluthrin-based SR to reduce ABV infection incidence over 2 y in a human cohort in Iquitos, Peru.