In vitro assessment of artesunate, artemether and amodiaquine susceptibility and molecular analysis of putative resistance-associated mutations of Plasmodium falciparum from São Tomé and Príncipe

Objective To evaluate the basal in vitro responses of Plasmodium falciparum isolates collected in The Democratic Republic of São Tomé and Príncipe to artemether (ATH), artesunate (ATN) and amodiaquine (AMQ). Methods The prevalence of given single nucleotide polymorphisms in the pfmdr1, pfcrt, pftctp and pfATPase6 genes was assessed by PCR‐RFLP or DNA sequencing, and gene copy numbers were estimated by real‐time PCR. Results Mean IC50s to ATH and ATN were relatively low (1.12 nm and 0.58 nm, respectively). However, 10% of parasites displayed AMQ IC50 values above the accepted resistance threshold of 60 nm and there was a positive association between susceptibility to all three drugs (ATH vs. ATN: R = 0.84; ATH vs. AMQ: R = 0.68; ATN vs. AMQ: R = 0.72). Mutations in the pfcrt and pfmdr1 genes were highly prevalent, while only one synonymous polymorphism was detected in the pfATPase6 gene and no mutations were found in pftctp. All isolates harboured a single copy of the genes studied. Conclusions Artemisinin combination treatment in the São Tomé and Príncipe should be efficacious, although a significant number of AMQ‐resistant parasites were detected and the susceptibility to each drug was positively associated with that of the other two. Mutations in the pfcrt and pfmdr1 genes are near fixation, most likely because of high levels of chloroquine resistance, whereas only one protein type of the artemisinin resistance candidate, PfATPase6, was identified.     

Delivery of insecticide-treated net services through employer and community-based approaches in Kenya

BACKGROUND AND OBJECTIVES: Many approaches have been used to deliver insecticide-treated nets (ITNs) to African communities in different settings. Between 1992 and 2002, the African Medical and Research Foundation (AMREF), Kenya, used two ITN delivery models: the employer-based approach and the community-based approach. These two approaches have never been compared in order to inform their potential for future ITN delivery. We aimed to (1) compare the extent of ITN ownership, use and retreatment coverage in different population groups in the employer and community-based models and (2) identify options for improving people's acceptance and use of treatment/retreatment services. METHODS: Qualitative and quantitative methods for data collection and analysis. A total of 2095 household heads were interviewed in the quantitative study, while purposively selected groups and key informants participated in the qualitative study. RESULTS: Net coverage (both treated and untreated nets) and retreatment rates with insecticides were significantly higher at employer-based sites (54.3%) than at community-based sites (35.0%). Bed net ownership has increased significantly since the start of AMREF interventions in 1998 in employer-based sites (from 27% to 61.1%); in community-based sites, it has either decreased (urban area, from 29.0% to 16.5%) or increased (rural area, from 17.0% to 49.1%). Retreatment rates in all sites were negatively influenced by the lack of information, cash and availability of insecticides. Satisfaction with the form of payment and services delivered was higher in employer-based sites. This was attributed to employers providing credit for the purchase of nets and retreatment kits and the employers' medical teams giving information on malaria and making follow-up visits on workers who fell ill. CONCLUSIONS: Employer-based delivery of ITNs was more successful than community-based delivery in attaining both high coverage with ITNs and higher rates of net retreatment. Methods used for the retreatment of nets, forms of payment and communication strategies should be convenient to communities. Organized community groups may continue to play an important role in remote rural areas.     

云南省恶性疟治疗研究现状

回顾了近40a来云南省对治疗恶性疟研究的疗效判定标准、抗性判定标准、病例入选标准和排除标准、病例观察方法以及实验室血液和生化指标选择,描述了5个单方和15个联合用药的效果观察结果,认为近年来云南的恶性疟原虫对氯喹的抗性仍然维持较高的水平;萘酚喹的治愈率高但是其临床即时效果不明显;蒿甲醚与本芴醇联用的效果最好;复方蒿甲醚和青蒿琥酯＋萘酚喹两配伍的治愈率、平均退热时间和平均无性体原虫清除时间均相似,是复方中较好的;青蒿素栓可首选与甲氟喹500mg伍用;青蒿琥酯与苯勿醇伍用的治愈率高达100％但是平均退热时间较长（仅次于苯勿醇单用）．对方法学按照目前国际流行的GCP进行了初步评价,针对存在的问题建议即按照GCP的要求建立云南省的恶性疟治疗效果评价标准方案和监查的标准规程（SOP）,建立必要的抗疟药临床实验基地,对常用的药物开展纵向敏感性观察、应用现代成熟的分子生物学方法为效果判断提供准确的数据．     

A randomized, controlled trial of artemisinin-piperaquine vs dihydroartemisinin-piperaquine phosphate in treatment of falciparum malaria

Objective:The study aimed to evaluate and compare the efficacy and safety of dihydroartemisininpiperaquine phosphate(Artekin) and artemisinin-piperaquine(Artequick) in the treatment of uncomplicated falciparum malaria.Methods:A total of 103 uncomplicated falciparum malaria patients were enrolled and randomly assigned to two groups:52 cases in the Artequick group,and 51 cases in the Artekin group.The patients in the Artequick group were administered with Artequick,twice in 24 h,whereas the patients in the...     

疟疾高度流行区回国人员的疟疾防制对策研究

目的探讨深圳市赴疟疾高度流行区回国人员的疟疾综合防制对策,为进一步加强我市的疟疾防制工作提供科学依据。方法对我市某高新企业赴疟疾高度流行区外派人员进行出国前健康教育、出国间药物预防和回国后健康排查并对该防制对策的效果进行分析研究。结果在疟疾相关知识健康教育前后,涉外员工的教育依从性和疟疾相关知识水平有显著提高,其中问卷回收率(χ2=21.024,ν=1,P<0.001)、疫区知识正确性(χ2=21.213,ν=1,P<0.001)和态度行为正确性(χ2=15.142,ν=1,P<0.001)增高明显。被干预人员的预防药物使用率逐年上升,疟疾发病率维持在较低水平。疟疾快速筛查方法与病原学检查结果符合率高,有助于病例的早期诊断和治疗。结论深圳市针对从疟疾高度流行区回国人员的疟疾防制对策为我市和其他涉外交流频繁地区的疟疾防制提供了重要的工作经验。     

Severe malaria and concomitant bacteraemia in children admitted to a rural Mozambican hospital

Objectives  To describe the prevalence, aetiology and prognostic implications of coexisting invasive bacterial disease in children admitted with severe malaria in a rural Mozambican Hospital.
Methods  Retrospective study of data systematically collected from June 2003 to May 2007 in a rural Mozambican hospital, from all children younger than 5 years admitted with severe malaria.
Results  Seven thousand and forty-three children were admitted with a diagnosis of malaria. 25.2% fulfilled the criteria for severe malaria. 5.4% of the children with severe malaria and valid blood culture results had a concomitant bacteraemia. Case fatality rates of severe malaria cases rose steeply when bacteraemia was also present (from 4.0% to 22.0%, P  < 0.0001), and bacteraemia was an independent risk factor for death among severe malaria patients (adjusted OR 6.2, 95% CI 2.8–13.7, P  = 0.0001). Streptococcus pneumoniae , Gram-negative bacteria, Staphilococcus aureus and non-typhoid Salmonella (NTS) were the most frequently isolated microorganisms among severe malaria cases. Their frequency and associated case fatality rates (CFR) varied according to age and to syndromic presentation. Streptococcus pneumoniae had a relatively low CFR, but was consistently associated with severe malaria syndromes, or anaemia severity groups. No clear-cut relationship between malarial anaemia and NTS bacteraemia was found.
Conclusions  The coexistence of malaria and invasive bacterial infections is a frequent and life-threatening condition in many endemic African settings. In Mozambique, S. pneumoniae is the leading pathogen in this interaction, possibly as a consequence of the high HIV prevalence in the area. Measures directed at reducing the burden of both those infections are urgently needed to reduce child mortality in Africa.     

The development of the RTS,S malaria vaccine candidate: challenges and lessons

RTS,S is the world's most advanced malaria vaccine candidate and is intended to protect infants and young children living in malaria endemic areas of sub-Saharan Africa against clinical disease caused by Plasmodium falciparum . Recently, a pivotal Phase III efficacy trial of RTS,S began in Africa. The goal of the programme has been to develop a vaccine that will be safe and effective when administered via the Expanded Program for Immunization (EPI) and significantly reduce the risk of clinically important malaria disease during the first years of life. If a similar reduction in the risk of severe malaria and other important co-morbidities associated with malaria infection can be achieved, then the vaccine could become a major new tool for reducing the burden of malaria in sub-Saharan Africa. Encouraging data from the ongoing phase II programme suggest that these goals may indeed be achievable. This review discusses some of the unique challenges that were faced during the development of this vaccine, highlights the complexity of developing new vaccine technologies and illustrates the power of partnerships in the ongoing fight against this killer disease.