高度疟疾流行区快速控制疟疾试验

[目的]探索在高度疟疾流行区快速控制疟疾的策略与方法.[方法]2004-2005两年期间,选择柬埔寨石居省疟疾高度流行区及其周边地带作为灭源灭疟试验区,共62个自然村21 343人口.在对当地疟疾流行情况进行了细致调查的基础上,采取三项主要灭源措施:①疟疾现症病人采用复方青蒿素(Artequick,ATQ)方案治疗,发热病人亦以此作假定性治疗;②儿童带虫率≥20%的17个村采用ATQ方案进行一次全民治疗;③儿童带虫率≥6%的27个村采用低剂量伯氨喹全民服药,每10d 1次,连续6个月.组织村抗疟员执行以上灭源措施.监测17个疫源村的人群带虫率,每6个月监测1次.[结果]采取灭源措施2年后,儿童带虫率从55.8%下降为5.3%:其中恶性疟带虫率由37.0%下降为2.3%;间日疟加三日疟带虫率由18.9%下降为3.0%;儿童恶性疟配子体带虫率由13.1%下降为1.2%.有8个村儿童恶性疟带虫率由采取措施前的平均46.5%下降至0.成人带虫率的改变与儿童带虫率改变相似,由46.5%降为6.3%;恶性疟带虫率由采取措施前的平均34.2%下降为2.5%,间日疟加三日疟带虫率由12.3%降为3.8%.[结论]灭源灭疟法有别于以控制蚊媒为主的传统方法,是一种又快又省钱的新方法和新策略,可在较短时间内扭转疟疾的高度流行,直至彻底消灭疟疾,值得在广大高疟区推广应用.     

Do social statuses affect the startle reflex in male mice?

Usual housing conditions lead to dominance hierarchy forming between male mice. The situation produces physiological and behavioural differences between dominants and subordinates. The goal of the present study was to assess stress responses, and possible changes in prepulse inhibition (PPI) of the startle reflex in dominant and subordinate male mice. Three weeks of daily social interactions led to stable aggressive dominance in 11 pairs of male NMRI mice. Stress levels were assessed by measuring faecal corticosterone metabolites (FCM), a non-invasive technique for monitoring hormonal changes in response to specific situations, with repeated sampling of each animal. The analysis of FCM levels showed greater stress in subordinate males at the beginning of the experiment, as the hierarchy was being established, but by the end of the experiment, FCM levels were reduced and similar in both dominants and subordinates. No significant differences were found in the startle response or PPI.     

Wildlife Reservoir for Hepatitis E Virus,Southwestern France

Pigs are a reservoir for hepatitis E virus (HEV). To determine the relative contribution of game to the risk for human HEV infection in southwestern France, we tested wildlife samples. HEV RNA was in 3.3% of wildlife livers, indicating that in this region, eating game meat is as risky as eating pork.     

Discovering disease-causing pathogens in resource-scarce Southeast Asia using a global metagenomic pathogen monitoring system

Understanding the regional pathogen landscape and surveillance of emerging pathogens is key to mitigating epidemics. Challenges lie in resource-scarce settings, where outbreaks are likely to emerge, but where laboratory diagnostics and bioinformatics capacity are limited. Using metagenomic next-generation sequencing (mNGS), we identified a variety of vector-borne, zoonotic, and emerging pathogens responsible for undifferentiated fevers in a periurban population in Cambodia. From March 2019 to October 2020, we enrolled 464 febrile patients (and 23 afebrile persons) aged 6 mo to 65 y presenting to a large periurban hospital in Cambodia. We collected sera and prepared sequencing libraries from extracted pathogen RNA for unbiased metagenomic sequencing and subsequent bioinformatic analysis on the global cloud-based platform, CZID (“IDseq”). We employed multivariable regression models to evaluate pathogen risk factors associated with undifferentiated febrile illness. mNGS identified vector-borne pathogens as the largest clinical category with dengue virus (124 of 489) as the most abundant pathogen. Underappreciated zoonotic pathogens, such as Plasmodium knowlesi, leptospirosis, and coinfecting HIV were also detected. Early detection of chikungunya virus presaged a larger national outbreak of more than 6,000 cases. Pathogen-agnostic mNGS investigation of febrile persons in resource-scarce Southeast Asia is feasible and revealing of a diverse pathogen landscape. Coordinated and ongoing mNGS pathogen surveillance can better identify the breadth of endemic, zoonotic, or emerging pathogens and deployment of rapid public health response.

A global pathogen surveillance network can best identify emerging and underlying pathogens if it employs pathogen-agnostic detection methods, such as metagenomic next-generation sequencing (mNGS), and is decentralized to include low-resource settings that are often biodiversity hotspots at increased risk for disease outbreaks (1–3). Lack of diagnostics in these areas makes undifferentiated febrile illnesses difficult to diagnose and treat, much less confirm and report for global public health awareness. In Southeast Asia, where a quarter of the world’s population resides, rapid but heterogeneous economic development juxtaposes low-resource and high-resource areas, causing high cross-border mobility of persons for economic opportunities. In Cambodia and Laos, laboratory testing for nonmalarial fevers is limited, particularly in rural and periurban areas where simple diagnostics like dengue rapid tests may not be available (4). In many instances, healthcare providers make diagnoses and empiric treatment decisions based on symptoms, so the responsible pathogen is rarely identified.Syndromic diagnosis is an epidemiological pitfall in Southeast Asia because the true scope of pathogen diversity remains poorly defined. From limited decade-old surveillance data of febrile Cambodians, Plasmodium infections made up more than 50% of the responsible pathogens followed by pathogenic Leptospira (9.4%), influenza virus (8.9%), and dengue virus (DENV) (6.3%) (5). In a separate serosurvey, one-third of febrile Cambodian patients had antibodies to rickettsiae that cause scrub typhus (via chiggers containing Orientia tsutsugamushi), endemic typhus (via rat fleas Xenopsylla cheopia carrying Rickettsia typhi), spotted fever (via ticks carrying Rickettsia rickettsii), and murine typhus (via cat fleas Ctenocephalides felis carrying Rickettsia felis) (6, 7). Entomological studies of field-collected ticks, mosquitos, and fleas in Cambodia have revealed high biodiversity of potential disease-carrying vectors, including underappreciated Bartonella spp. (8, 9). Other serosurveys of bats, domestic pigs, and birds in Cambodia demonstrated the presence of antibodies to other zoonotic viruses, including Nipah virus, hepatitis E, Japanese encephalitis virus, and West Nile virus with potential for spillover into the human population (10–12).In these settings of high pathogen diversity, monitoring with pathogen-agnostic tools, such as mNGS, is ideal but typically not available in-country to provide results within an actionable time frame. Examples of mNGS identifying pathogens in patients are limited to clinical research programs in developed countries (13–15). However, it is clear that broadly applied and timely mNGS in any population can lead to a better understanding of the overall pathogen landscape, which has direct implications for disease containment methods in the event of an outbreak (16, 17). Here, as an initial step in a low-resource setting in Asia, we describe implementation of mNGS surveillance using an open-source cloud-based bioinformatics tool to identify pathogens in sera from febrile individuals in periurban Cambodia.     

青蒿素哌喹片治疗间日疟62例临床报道

[目的]观察青蒿素哌喹片(Aaequick)治疗间日疟的有效性、安全性及临床剂量.[方法]对62例间日疟患者采用成人总量4片Artequick 2 d疗程的给药方案治疗,观察近期治愈率、近期复发率以及平均原虫复燃天数等有效性指标,并评价其安全性.[结果]62例患者经治疗后临床症状较快缓解,平均原虫转阴时间为(60.7±23.9)h,平均退热时间为(14.1±7.8)h,其中54例完成28 d观察,近期治愈率为94.4%(51/54例),近期复发率为5.6%(3/54例).本组病例对Artequick的耐受性良好,仅有少数病人出现恶心、呕吐;且为自限性;比较服药前与服药后第7天的血液、生化、心电图等指标,未发现Artequick片有明显的毒性.[结论]青蒿素哌喹片治疗间日疟,具有高效、速效、副反应少等优点,值得,临床推广应用.     

青蒿素哌喹片治疗无并发症恶性疟的剂量探索试验

目的探索青蒿素哌喹片治疗无并发症恶性疟的安全有效的适宜剂量。方法收治7～65岁男性和女性病人共100例,按区组随机化方案分成2组,成人总量1400 mg组年龄(22±s12)岁,1750 mg组年龄(21±12)岁。分别于0h和24h给药一次,比较2组的平均原虫转阴和退热时间、28d治愈率及原虫复燃率。结果2组的平均原虫转阴时间分别是(61±19)h和(57±21)h,平均退热时间为(20±15)h和(18±10)h,P>0.05;28 d治愈率是80%和96%,原虫复燃率为20%和4%,总量1750 mg组显著优于1400 mg组(P<0.05)。2组耐受性均良好,未发现明显的不良反应。结论推荐青蒿素哌喹片的临床治疗剂量为总量1750 mg,每日1次,分2d服完为1个疗程。     

KCa2 channels transiently downregulated during spatial learning and memory in rats

Small‐conductance calcium‐activated potassium channels (K_Ca2) are essential components involved in the modulation of neuronal excitability, underlying learning and memory. Recent evidence suggests that K_Ca2 channel activity reduces synaptic transmission in a postsynaptic NMDA receptor‐dependent manner and is modulated by long‐term potentiation. We used radioactive in situ hybridization and apamin binding to investigate the amount of K_Ca2 subunit mRNA and K_Ca2 proteins in brain structures involved in learning and memory at different stages of a radial‐arm maze task in naive, pseudoconditioned, and conditioned rats. We observed significant differences in K_Ca2.2 and K_Ca2.3, but not K_Ca2.1 mRNA levels, between conditioned and pseudoconditioned rats. K_Ca2.2 levels were transiently reduced in the dorsal CA fields of the hippocampus, whereas K_Ca2.3 mRNA levels were reduced in the dorsal and ventral CA fields of the hippocampus, entorhinal cortex, and basolateral amygdaloid nucleus in conditioned rats, during early stages of learning. Levels of apamin‐binding sites displayed a similar pattern to K_Ca2 mRNA levels during learning. Spatial learning performance was positively correlated with levels of apamin‐binding sites and K_Ca2.3 mRNA in the dorsal CA1 field and negatively correlated in the dorsal CA3 field. These findings suggest that K_Ca2 channels are transiently downregulated in the early stages of learning and that regulation of K_Ca2 channel levels is involved in the modification of neuronal substrates underlying new information acquisition. © 2009 Wiley‐Liss, Inc.     

Decreasing pfmdr1 Copy Number Suggests that Plasmodium falciparum in Western Cambodia Is Regaining In Vitro Susceptibility to Mefloquine

Dihydroartemisinin-piperaquine is the current frontline artemisinin combination therapy (ACT) for Plasmodium falciparum malaria in Cambodia but is now failing in several western provinces. To investigate artesunate plus mefloquine (AS+MQ) as a replacement ACT, we measured the prevalence of multiple pfmdr1 copies—a molecular marker for MQ resistance—in 844 P. falciparum clinical isolates collected in 2008 to 2013. The pfmdr1 copy number is decreasing in Western Cambodia, suggesting that P. falciparum is regaining in vitro susceptibility to MQ.