Immunological markers of childhood fevers in an area of intense and perennial malaria transmission.

In order to describe presumed paediatric malaria on a cell-immunological basis, the soluble receptors of IL-2 (sIL-2R) and tumour necrosis factor (sTNF-R55 and sTNF-R75) were quantified in highly exposed young Tanzanian children. Sera were obtained from 66 acute and 72 reported febrile patients during health post consultations and follow-ups and from 68 community controls. Levels of sIL-2R, sTNF-R55 and sTNF-R75 were significantly elevated during fever attacks, especially in very young children. Soluble TNF-R75 levels were most stable and those of sTNF-R55 least. Levels of sTNF-R55 were related to the magnitude of fever and thus appeared to reflect attack severity. Levels of sTNF-R75 were highly significantly associated with parasite density, indicating that this response is malaria-specific. The present study indicates that sTNF-R75 levels could become a useful immunological tool in malaria intervention studies, as they reflect changes in malaria-specific immune responses. Future studies should validate this potential in different endemic settings.     

Interferon-γ is essential for the development of cerebral malaria

Infection with Plasmodium berghei ANKA (PbA) causes fatal cerebral malaria (CM). While a pathogenic role for tumor necrosis factor (TNF) has been established, we asked whether a disruption of interferon-γ (IFN-γ) signaling would modulate CM. We demonstrate here that IFN-γR-deficient mice are completely protected from CM. PbA-induced release of TNF and up-regulation of endothelial intercellular adhesion molecule (ICAM)-1 expression, recruitment of mononuclear cells, and cerebral microvascular damage with vascular leakage occur only in wild-type mice. Protected mice die at a later time of severe anemia and overwhelming parasitemia. Resistance to CM in IFN-γR-deficient mice is associated with reduced serum TNF levels, reduced interleukin-12 expression in the brain and increased T-helper 2 cytokines. In conclusion, IFN-γ is apparently required for PbA-induced endothelial ICAM-1 up-regulation and subsequent microvascular pathology, resulting in fatal CM. In the absence of IFN-γ signaling, ICAM-1 and TNF up-regulation is reduced; hence, PbA infection fails to cause fatal CM.     

海南省琼中县高疟区应用磷酸萘酚喹控制疟疾的效果

目的 评估在较大的范围内使用磷酸萘酚喹控制疟疾的效果,为今后该药用于控制疟疾提供依据。方法 在季节性抗疟控制传染源的用药上,对春季和秋季抗疟的集体服药村庄,一律使用磷酸萘酚喹一天疗法,代替哌喹 防Ⅱ 伯喹两天疗法,从首次服药的第七天起,由卫生院防保人员和村医,每隔七天到各村巡诊,发现“四热”病人采血送检,掌握用药前后的疫情动态。结果 据疫情报告统计,2000年全年“四热”血检率达10％以上,血检阳性率0．62％、居民带虫率0．05％、年带虫发病率(API)1．5‰,与1999年对比,分别下降55．83％、93．93％、33．78％,发病村(队)由1999年的180个减至109个,减少39．44％,且无明显副反应。结论 琼中县高疟区居民集体服药使用磷酸萘酚喹控制疟疾流行效果较为显,值得继续应用作进一步的评估。     

江苏省灭疟后期疟疾流行态势分析

目的 了解江苏省灭疟后期疟疾流行特点。方法 收集全省各县１９８９－２０００年疟疾疫情资料,对不同年份、不同地区的发病率或阳性率进行相关分析或率的显著性检验。结果 全省年发病率变化趋势与两种按蚊共存地区的发病率呈一致关系,中华按蚊地区疟疾发病稳定在较低水平,平均年发病率为 ０．１０／万;而两种按蚊共存地区平均发病率为１．８６／万,明显高于中华按蚊单一区（ｐ＜０．０１）,且有向毗邻地区扩散的趋势。本地居民友热病人血检阳性率０．０６％,流动人口发热病人血检阳性率０、５５％,两者间有显著性差异（ｐ＜０．０１）。ＩＦＡ阳性率与发病率呈相关关系。结论 两种按蚊共存地区及其毗邻地区疟疾潜在流行的危险性较高,中华按蚊单一媒介地区出现较大流行和反复的可能性较小。     

A phase IIA extension study evaluating the effect of booster vaccination with a fractional dose of RTS,S/AS01E in a controlled human malaria infection challenge

BackgroundWe previously demonstrated that RTS,S/AS01_B and RTS,S/AS01_E vaccination regimens including at least one delayed fractional dose can protect against Plasmodium falciparum malaria in a controlled human malaria infection (CHMI) model, and showed inferiority of a two-dose versus three-dose regimen. In this follow-on trial, we evaluated whether fractional booster vaccination extended or induced protection in previously protected (P-Fx) or non-protected (NP-Fx) participants.Methods49 participants (P-Fx: 25; NP-Fx: 24) received a fractional (1/5th dose-volume) RTS,S/AS01_E booster 12 months post-primary regimen. They underwent P. falciparum CHMI three weeks later and were then followed for six months for safety and immunogenicity.ResultsOverall vaccine efficacy against re-challenge was 53% (95% CI: 37–65%), and similar for P-Fx (52% [95% CI: 28–68%]) and NP-Fx (54% [95% CI: 29–70%]). Efficacy appeared unaffected by primary regimen or previous protection status. Anti-CS (repeat region) antibody geometric mean concentrations (GMCs) increased post-booster vaccination. GMCs were maintained over time in primary three-dose groups but declined in the two-dose group. Protection after re-challenge was associated with higher anti-CS antibody responses. The booster was well-tolerated.ConclusionsA fractional RTS,S/AS01_E booster given one year after completion of a primary two- or three-dose RTS,S/AS01 delayed fractional dose regimen can extend or induce protection against CHMI.Clinical Trial Registration: NCT03824236.A video linked to this article can be found on the Research Data as well as Figshare https://figshare.com/s/ee025150f9d1ac739361     

细胞间黏附因子1(Ⅰ区)模拟肽的筛选及初步鉴定

目的 筛选表达细胞间黏附因子1（ICAM－1）（Ⅰ区）模拟肽的特异噬菌体克隆,为研制抗脑型疟黏附肽类药物奠定基础。方法 以抗ICAM－1（Ⅰ区）的单抗15．2为靶,采用亲和筛选法对噬菌体随机十二肽库进行3轮筛选,通过ELISA及竞争抑制试验初步鉴定了获得的噬菌体短肽与单抗15．2之间的结合特性。结果 从第3轮洗脱液中挑选20个噬菌体克隆进行夹心法ELISA检测,其中18个克隆OD值超过阴性对照2．1倍以上,阳性率达90％。竞争性ELISA试验表明多数阳性噬菌体与ICAM－1能竞争性地与15．2单抗结合。结论 阳性噬菌体表达的短肽可能是15．2单抗所识别的模拟表位。Ⅰ     

自然界郑州中华按蚊传疟媒介能量的研究

目的了解自然界郑州中华按蚊传播间日疟的潜在能力。方法采用媒介能量诸因素定量调查和运用数学模型的方法。结果计算出中华按蚊叮人率、人血指数、叮人习性、经产蚊比率、生殖营养周期、每日存活率、预期寿命、孢子增殖时间、有传疟性蚊的比率,预期传疟蚊寿命、媒介能量等参数值。结论每年7月下旬、8月上、中旬郑州中华按蚊的媒介能量最高,潜在存在着间日疟流行或暴发流行的可能。     

Severe malaria in African adults living in a seasonal endemic area

Objective This study investigates severe malaria in african adults living in a seasonal endemic area.Design: A prospective study of all adults admitted with severe malaria over 2 consecutive seasons: October 1990 till January 1991 and October 1991 till January 1992.Setting ICU (15 beds) of Hôpital Principal, Dakar, Sénégal.Patients 23 patients: 14 men and 9 women with a mean age of 30±3 years were included in the study; all fulfilled the 1990 WHO criteria for severe malaria.Results At admission, 12 patients were comatose (Glasgow Coma Scale<10), 7 had generalized convulsions. Parasitaemia was 135±52×10⁹/l. Biological indications of severity were as follows: hypophosphataemia <0.8 mmol/l in 14 cases, serum creatine phosphokinase >500 IU/l in 15 cases; and PaO₂<70 mmHg in 5 cases. Serum TNF levels, measured in 16 cases, were increased at 298.4±63.5 pg/ml, serum levels of IL-6 and IL-2SR were also elevated: 609.5±304.2 pg/ml and 297.6±35.6 pg/ml respectively. Circulating IgM and IgG antibodies were found in 14 out of 16 patients. Serum levels of TNF, IL-6 and IL-2SR correlated positively with each other. TNF and IL-2SR were also positively correlated to parasitaemia. Intravenous therapy with quinine at loading dose was favorable in 19 patients. Four patients died during the study, 3 from multiple organ failure.Conclusions: This work demonstrated that severe malaria in a seasonal endemic area displays original clinical features with a high rate of either cerebral malaria or multiple organ failure.     

蒙城县疟疾防治对策与效果评价

本文报告了蒙城县非稳定性单纯间日疟流行区,从６０年代初到７０年代初曾发生过两次大面积暴发流行,７０年代中和８０年代初又发生三次较大流行。通过２４年来的积极防治,在采取“两根治、一预防、消灭传染源”为主的综合性防治和现症病人管理三个阶段不同对策后,使流行范围逐年缩小,疟疾发病大幅度下降,全县疟疾发病率从１９７０年的１６８３．８８／万,降至１９９７年的０．００９／万,并实现了连续１２年在１／万以下,１９９８年全县无疟疾疫情,达到了部颁基本消灭疟疾标准。