Spatio-Temporal Patterns in kdr Frequency in Permethrin and DDT Resistant Anopheles gambiae s.s. from Uganda

The planned upscaling of vector control strategies requires insight into the epidemiological consequences of vector resistance. Therefore, the pyrethroid and DDT resistance status of Anopheles gambiae s.l. was assessed in Uganda from 2004 to 2006, and spatial and seasonal variations in knockdown resistance (kdr) frequencies were analyzed in terms of epidemiological significance. Anopheles gambiae s.l. was DDT and pyrethroid resistant in central and eastern Uganda. The L1014S kdr allele frequencies varied from 3% to 48% in An. gambiae s.s. Although the homozygous resistant genotype was the most prevalent genotype among survivors, the genotypes could not entirely explain the bioassay results. In the dry season, the kdr frequency was significantly higher in Plasmodium falciparum-infected mosquitoes, indicating that mosquitoes bearing a kdr mutation have a better adult survival, hence a higher likelihood of becoming infectious. This study showed that kdr might have an epidemiological impact that could jeopardize the vector control strategies

Malaria transmission and vector behaviour in a forested malaria focus in central Vietnam and the implications for vector control

BACKGROUND: In Vietnam, malaria is becoming progressively restricted to specific foci where human and vector characteristics alter the known malaria epidemiology, urging for alternative or adapted control strategies. Long-lasting insecticidal hammocks (LLIH) were designed and introduced in Ninh Thuan province, south-central Vietnam, to control malaria in the specific context of forest malaria. An entomological study in this specific forested environment was conducted to assess the behavioural patterns of forest and village vectors and to assess the spatio-temporal risk factors of malaria transmission in the province. METHODS: Five entomological surveys were conducted in three villages in Ma Noi commune and in five villages in Phuoc Binh commune in Ninh Thuan Province, south-central Vietnam. Collections were made inside the village, at the plot near the slash-and-burn fields in the forest and on the way to the forest. All collected mosquito species were subjected to enzyme-linked immunosorbent assay (ELISA) to detect Plasmodium in the head-thoracic portion of individual mosquitoes after morphological identification. Collection data were analysed by use of correspondence and multivariate analyses. RESULTS: The mosquito density in the study area was low with on average 3.7 anopheline bites per man-night and 17.4 culicine bites per man-night. Plasmodium-infected mosquitoes were only found in the forest and on the way to the forest. Malaria transmission in the forested malaria foci was spread over the entire night, from dusk to dawn, but was most intense in the early evening as nine of the 13 Plasmodium positive bites occurred before 21H. The annual entomological inoculation rate of Plasmodium falciparum was 2.2 infective bites per person-year to which Anopheles dirus s.s. and Anopheles minimus s.s. contributed. The Plasmodium vivax annual entomological inoculation rate was 2.5 infective bites per person-year with Anopheles sawadwongporni, Anopheles dirus s.s. and Anopheles pampanai as vectors. CONCLUSION: The vector behaviour and spatio-temporal patterns of malaria transmission in Southeast Asia impose new challenges when changing objectives from control to elimination of malaria and make it necessary to focus not only on the known main vector species. Moreover, effective tools to prevent malaria transmission in the early evening and in the early morning, when the treated bed net cannot be used, need to be developed

The insecticide resistance status of malaria vectors in the Mekong region

<p>Abstract</p> <p>Background</p> <p>Knowledge on insecticide resistance in target species is a basic requirement to guide insecticide use in malaria control programmes. Malaria transmission in the Mekong region is mainly concentrated in forested areas along the country borders, so that decisions on insecticide use should ideally be made at regional level. Consequently, cross-country monitoring of insecticide resistance is indispensable to acquire comparable baseline data on insecticide resistance.</p> <p>Methods</p> <p>A network for the monitoring of insecticide resistance, MALVECASIA, was set up in the Mekong region in order to assess the insecticide resistance status of the major malaria vectors in Cambodia, Laos, Thailand, and Vietnam. From 2003 till 2005, bioassays were performed on adult mosquitoes using the standard WHO susceptibility test with diagnostic concentrations of permethrin 0.75% and DDT 4%. Additional tests were done with pyrethroid insecticides applied by the different national malaria control programmes.</p> <p>Results</p> <p><it>Anopheles dirus s.s</it>., the main vector in forested malaria foci, was susceptible to permethrin. However, in central Vietnam, it showed possible resistance to type II pyrethroids. In the Mekong delta, <it>Anopheles epiroticus </it>was highly resistant to all pyrethroid insecticides tested. It was susceptible to DDT, except near Ho Chi Minh City where it showed possible DDT resistance. In Vietnam, pyrethroid susceptible and tolerant <it>Anopheles minimus s.l</it>. populations were found, whereas <it>An. minimus s.l</it>. from Cambodia, Laos and Thailand were susceptible. Only two <it>An. minimus s.l</it>. populations showed DDT tolerance. <it>Anopheles vagus </it>was found resistant to DDT and to several pyrethroids in Vietnam and Cambodia.</p> <p>Conclusion</p> <p>This is the first large scale, cross-country survey of insecticide resistance in <it>Anopheles </it>species in the Mekong Region. A unique baseline data on insecticide resistance for the Mekong region is now available, which enables the follow-up of trends in susceptibility status in the region and which will serve as the basis for further resistance management. Large differences in insecticide resistance status were observed among species and countries. In Vietnam, insecticide resistance was mainly observed in low or transmission-free areas, hence an immediate change of malaria vector control strategy is not required. Though, resistance management is important because the risk of migration of mosquitoes carrying resistance genes from non-endemic to endemic areas. Moreover, trends in resistance status should be carefully monitored and the impact of existing vector control tools on resistant populations should be assessed.</p

False positive circumsporozoite protein ELISA: a challenge for the estimation of the entomological inoculation rate of malaria and for vector incrimination

<p>Abstract</p> <p>Background</p> <p>The entomological inoculation rate (EIR) is an important indicator in estimating malaria transmission and the impact of vector control. To assess the EIR, the enzyme-linked immunosorbent assay (ELISA) to detect the circumsporozoite protein (CSP) is increasingly used. However, several studies have reported false positive results in this ELISA. The false positive results could lead to an overestimation of the EIR. The aim of present study was to estimate the level of false positivity among different anopheline species in Cambodia and Vietnam and to check for the presence of other parasites that might interact with the anti-CSP monoclonal antibodies.</p> <p>Methods</p> <p>Mosquitoes collected in Cambodia and Vietnam were identified and tested for the presence of sporozoites in head and thorax by using CSP-ELISA. ELISA positive samples were confirmed by a <it>Plasmodium </it>specific PCR. False positive mosquitoes were checked by PCR for the presence of parasites belonging to the Haemosporidia, Trypanosomatidae, Piroplasmida, and Haemogregarines. The heat-stability and the presence of the cross-reacting antigen in the abdomen of the mosquitoes were also checked.</p> <p>Results</p> <p>Specimens (N = 16,160) of seven anopheline species were tested by CSP-ELISA for <it>Plasmodium falciparum </it>and <it>Plasmodium vivax </it>(Pv210 and Pv247). Two new vector species were identified for the region: <it>Anopheles pampanai </it>(<it>P. vivax</it>) and <it>Anopheles barbirostris </it>(<it>Plasmodium malariae</it>). In 88% (155/176) of the mosquitoes found positive with the <it>P. falciparum </it>CSP-ELISA, the presence of <it>Plasmodium </it>sporozoites could not be confirmed by PCR. This percentage was much lower (28% or 5/18) for <it>P. vivax </it>CSP-ELISAs. False positive CSP-ELISA results were associated with zoophilic mosquito species. None of the targeted parasites could be detected in these CSP-ELISA false positive mosquitoes. The ELISA reacting antigen of <it>P. falciparum </it>was heat-stable in CSP-ELISA true positive specimens, but not in the false positives. The heat-unstable cross-reacting antigen is mainly present in head and thorax and almost absent in the abdomens (4 out of 147) of the false positive specimens.</p> <p>Conclusion</p> <p>The CSP-ELISA can considerably overestimate the EIR, particularly for <it>P. falciparum </it>and for zoophilic species. The heat-unstable cross-reacting antigen in false positives remains unknown. Therefore it is highly recommended to confirm all positive CSP-ELISA results, either by re-analysing the heated ELISA lysate (100°C, 10 min), or by performing <it>Plasmodium </it>specific PCR followed if possible by sequencing of the amplicons for <it>Plasmodium </it>species determination.</p

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Patient-controlled intravenous analgesia as an alternative to epidural analgesia during labor: questioning the use of the short-acting opioid remifentanil. Survey in the French part of Belgium (Wallonia and Brussels).

Childbirth ranks among the most intense experiences of acute pain. Neuraxial analgesia (i.e. epidural or combined spinal-epidural technique) is the most effective way to relieve that pain but it is contraindicated or impossible to perform for some parturients. We designed a survey of the current use of analgesic alternatives to epidural analgesia (EA) for labor pain, specifically the use of opioid patient-controlled intravenous analgesia (PCIA), in the French part of Belgium (Wallonia and Brussels). A questionnaire was mailed to the departmental chair of the hospitals with an obstetric unit, both in university and non-university centers (total of 53 centers). The questionnaire evaluated the availability of EA, the alternatives used when EA was contraindicated, the use of opioid-based PCIA for labor analgesia as well as opioid preference and doses, and finally the reasons for not using opioid PCIA. The response rate was 67.5% (36 centers). Among the responding hospitals, EA was available for 68% (range 25-85%) of labors and deliveries. When EA was not available or contraindicated, a parenteral opioid (piritramide, tramadol or pethidine) was proposed in 19% (7/36) of the centers, Entonox in 11% (4/36), a pudendal block by obstetricians in 28% (10/36) and non-pharmacologic alternatives (i.e. hypnosis, sophrology, baths and massages) in 19% (7/36). In 28% (10/36) of the centers however, no analgesic alternative was proposed. Opioid PCIA was employed in 36% (13/36) of the centers and for an additional 11% (4/36) only in case of intrauterine death. Remifentanil was the first choice (76.5% of the PCIA), followed by sufentanil (23.5%). Other opioids (piritramide, morphine, fentanyl) and ketamine were also administered by PCIA. Forty-five percents of the centers reported never using opioid PCIA by either lack of knowledge (7%), fear of maternal or fetal side effects (48%) and unability to provide a correct supervision of the parturient during PCIA use (48%), opposition from the pediatricians or obstetricians (17%) or because they considered the technique as ineffective to relieve labor pain (17%). In conclusion, the survey demonstrated that, when EA is contraindicated, systemic opioid administered by PCIA is used in almost half of the centers (47%) and that remifentanil is the first choice, particularly when a live birth is expected

Epidural neostigmine combined with sufentanil provides balanced and selective analgesia in early labor

BACKGROUND: This study evaluated the efficacy of an epidural single dose of neostigmine combined with sufentanil to provide selective and balanced analgesia at the beginning of labor. METHODS: After informed consent, 125 healthy parturients were randomly allocated to receive, after a test dose, a single injection of either epidural sufentanil 20 micrograms (minimal analgesic dose) or 10 micrograms or a combination of sufentanil 10 micrograms with neostigmine 250, 500, or 750 micrograms in a total volume of 12 ml. Pain scores were recorded at regular intervals to determine onset and duration of analgesia. Maternal and fetal vital parameters as well as side effects were closely monitored. RESULTS: Parturients did not differ concerning demographic data. Epidural neostigmine 500 micrograms with sufentanil 10 micrograms produced effective analgesia (visual analog scale <30 mm within 10 min in 72% parturients and within 15 min in 85% parturients; average duration of 119 min, confidence interval 96-142 min) that was as effective as epidural sufentanil 20 micrograms. Epidural combination with neostigmine 250 micrograms was ineffective, whereas 750 micrograms did not produce higher effect than 500 micrograms. No motor block was recorded. Maternal and fetal vital parameters remained stable during labor. CONCLUSIONS: Epidural combination of neostigmine 500 micrograms (e.g., 6-7 micrograms/kg) with sufentanil 10 micrograms provides similar duration of analgesia as epidural sufentanil 20 micrograms and allows effective and selective analgesia devoid of side effects in the first stage of labor

Evaluation of pregabalin as an adjuvant to patient-controlled epidural analgesia during late termination of pregnancy

INTRODUCTION:: Late termination of pregnancy combines psychological distress with severe physical pain. The present study evaluated the benefit of adding oral pregabalin to epidural analgesia during this procedure. METHODS:: Healthy women were randomly allocated to receive either oral pregabalin 150 mg/12 h or prazepam 10 mg/12 h at the induction of the late termination of pregnancy procedure. When they felt abdominal pain (numerical rating scale ranging from 0 [no pain] to 100 [worst pain possible]), patient-controlled epidural analgesia was activated and set to deliver ropivacaine 0.1% with sufentanil 0.25 μg/ml, 5 ml/h with a bolus dose of 5 ml/30 min. Rescue analgesia was available as needed by administration of 10 ml ropivacaine 0.1% (pain score less than 60/100) or 0.2% (at least 60/100). The primary outcome was the consumption of epidural analgesics. RESULTS:: Forty-eight patients participated in the study. Demographic and obstetric data were similar. Pregabalin reduced total ropivacaine consumption 11.3 ± 3.2 mg/h (mean ± SD) versus 15.1 ± 4.9 mg/h in the prazepam group (P = 0.005), an effect related to a decrease in the need for rescue analgesia. In the pregabalin group, fewer women asked for rescue dose (75 vs. 96%; P = 0.048), and the number of rescue doses per patient was reduced (1 [0-2] vs. 2 [1-3]); median [interquartile range], P = 0.005), particularly the need for ropivacaine 0.2%. DISCUSSION:: This is the first study considering the use of pregabalin for labor pain associated with late termination of pregnancy, showing that pregabalin 150 mg/12 h is a helpful adjuvant to epidural analgesia. Modulation of both visceral sensitization and affective component of pain may contribute to the benefits observed

Clonidine versus sufentanil as an adjuvant to ropivacaine in patient-controlled epidural labour analgesia: A randomised double-blind trial.

BACKGROUND: Adjuvants to local anaesthetics for epidural labour analgesia are useful if they reduce side-effects or personnel requirements. Epidural clonidine improves analgesia and provides a significant local anaesthetic-sparing effect. OBJECTIVE: To compare the number of rescue doses administered by the anaesthesiologist when clonidine or sufentanil is added to epidural ropivacaine. DESIGN: A randomised double-blind trial. SETTING: Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium, from June 2009 to June 2010. PATIENTS: One hundred and ninety-five women in labour. INTERVENTION: Epidural analgesia initiated with 10 ml ropivacaine 0.1%, women randomised to receive patient-controlled epidural analgesia (5 ml demand bolus, 15 min lockout) with ropivacaine 0.1% and sufentanil 0.25 μg ml⁻¹ (RS group; n = 65), or ropivacaine 0.1% and clonidine 1.5 μg ml⁻¹ (RC1.5 group; n = 65) or ropivacaine 0.1% and clonidine 3 μg ml⁻¹ (RC3 group; n = 65). Rescue analgesia was available as needed – 10 ml ropivacaine 0.1% (numerical rating scale <6/10) or ropivacaine 0.2% (numerical rating scale ≥6/10). MAIN OUTCOME: Comparison of the total number of rescue doses. RESULTS: The total number of rescue doses was similar among the groups [median (interquartile range): 1 (0 to 1) in the RC1.5 group, 1 (1 to 2) in the RC3 group and 2 (1 to 2) in the RS group; overall P = 0.056]. However, fewer patients in both the RC1.5 and RC3 groups needed two or more rescue doses (25 and 29% versus 52% in the RS group, P = 0.01). The rate of instrumental delivery was higher in both clonidine groups (13 and 12% versus 0%, P = 0.03). Nausea was significantly less frequent in both the clonidine groups. Satisfaction scores, total ropivacaine consumption, maternal sedation, and hypotension and neonatal outcomes were similar among the groups. CONCLUSION: Compared with sufentanil 0.25 μg ml⁻¹, addition of clonidine (1.5 to 3 μg ml⁻¹) to patient-controlled epidural analgesia with ropivacaine 0.1% provided similar labour analgesia and a similar need for anaesthesiologist-administered rescue doses. Clonidine 3 μg ml⁻¹ did not offer any advantage over clonidine 1.5 μg ml⁻¹. The instrumentation rate was higher in both the clonidine groups