艾滋病合并马尔尼菲篮状菌病的研究进展

马尔尼菲篮状菌病是一种由马尔尼菲篮状菌引起的深部真菌病,易发于免疫功能缺陷和免疫功能障碍的人群。随着艾滋病患者的逐渐增多,马尔尼菲篮状菌的感染率也随之上升。该文从马尔尼菲篮状菌病的流行病学、临床表现、临床诊断和治疗综述了马尔尼菲篮状菌病的研究进展。     

巨噬细胞对马尔尼菲篮状菌免疫作用机制研究进展

马尔尼菲篮状菌(Talaromyces marneffei),旧称为马尔尼菲青霉菌(Penicillium marneffei),流行于东南亚和中国南部。法国Capponi等[1]在1956年从竹鼠体内分离的青霉菌属温控双相条件致病菌,室温25℃条件下表现为菌丝相,37℃环境下表现为酵母相,酵母相菌体具有致病性。马尔尼菲篮状菌病主要集中于免疫力低下人群,尤其HIV患者,若得不到有效的治疗,病死率极高[2,3]。近年来,感染T.marneffei发病率上升趋势明显[4],其传播途径最常见是经呼吸道吸入T.marneffei孢子导致感染。     

马尔尼菲篮状菌基因研究进展

温度依赖性双相真菌马尔尼菲篮状菌可致局限性或全身播散性感染,在东南亚以及我国南方,尤其是广西、广东有区域性流行。该菌主要感染免疫力低下的人群,是流行区艾滋病患者特征性的机会性感染。文中主要介绍马尔尼菲篮状菌的相关基础知识、基因研究历史进程以及综述马尔尼菲篮状菌在生长发育、双相转换、信号通路、细胞壁合成、细胞代谢、应激反应、热休克、色素、毒力及耐药方面的基因研究进展。     

不同交配型马尔尼菲篮状菌的抗真菌药物敏感性

马尔尼菲篮状菌是马尔尼菲篮状菌病的致病菌,具有不同交配型,且交配型分布具有地域差异。交配型是影响某些真菌药物敏感性的因素之一,但是否影响马尔尼菲篮状菌的药物敏感性不详。为了解马尔尼菲篮状菌交配型和其药物敏感性的关系,本研究检测了不同交配型马尔尼菲篮状菌对7种抗真菌药物的敏感性。结果显示,与MAT-1型马尔尼菲篮状菌相比,MAT-2型马尔尼菲篮状菌对伊曲康唑的敏感性较低,提示马尔尼菲篮状菌交配型可能与马尔尼菲唑类耐药相关。     

伏立康唑在马尔尼菲篮状菌感染中的应用进展

<正>马尔尼菲篮状菌感染是最常见的艾滋病相关机会性感染之一,是东南亚国家及我国南部省份艾滋病相关死亡的主要原因,若不及时诊治,其死亡率高达100%^[1]。目前对于马尔尼菲篮状菌感染的治疗首选为两性霉素B^[2],但其副作用大、不良反应多,导致许多患者都难以耐受,伏立康唑已成为其替代治疗的首选。本文对伏立康唑在马尔尼菲篮状菌感染中的应用进行综述。     

实时荧光定量PCR检测马尔尼菲篮状菌病组织样本中菌载量的研究

目的实时荧光定量PCR测定马尔尼菲篮状菌病组织样本中马尔尼菲篮状菌的载量。方法收集马尔尼菲篮状菌病患者的皮肤病理切片、淋巴结活检组织,提取总DNA,采用实时荧光定量PCR技术检测样本中马尔尼菲篮状菌载量。结果皮肤病理切片、淋巴结活检组织中马尔尼菲篮状菌载量阳性。病理切片平均菌载量3.01×10~4 copies(1.07×10~4~7.26×10~4 copies),淋巴结活检组织中马尔尼菲篮状菌载量4.68×10~5 copies。结论荧光定量PCR能高效检测皮肤病理切片、淋巴结活检组织中马尔尼菲篮状菌载量,对马尔尼菲篮状菌病诊断有一定的价值。     

马尔尼菲青霉的分子生物学研究进展

马尔尼菲青霉是一种主要累及免疫受损患者的条件致病性双相真菌,近年来随着HIV感染的增多,马尔尼菲青霉病发病率呈现逐年上升的趋势。国内外学者对马尔尼菲青霉及其致病机制进行了大量的研究,尤其是分子生物学方法的应用,使人们对马尔尼菲青霉的真菌学特点和马尔尼菲青霉病的发病机制有了更深入的了解,使早期诊疗成为可能。该文主要从分子流行病学、分子遗传学和分子生物学诊断方面对马尔尼菲青霉进行综述。     

MADLI-TOF MS自建库在马尔尼菲篮状菌快速鉴定中的应用

目的评价基质辅助激光解吸电离飞行时间质谱(MADLI-TOF MS)自建库对临床分离马尔尼菲篮状菌快速鉴定的能力。方法收集广州、玉林、防城港3个地区临床分离的马尔尼菲篮状菌,通过ITS区扩增测序进行菌种准确鉴定。菌株通过微型玻璃珠研磨结合甲酸/乙腈提取法预处理。通过采集建库菌株不同时间点、不同平板上菌丝相和酵母相菌落的质谱数据,建立包含马尔尼菲篮状菌超级图谱的自建库;并用非建库的马尔尼菲篮状菌及临床常见的真菌评估建立的自建库。结果建立了包含具有39个特征峰的马尔尼菲篮状菌超级图谱的自建库;用于评估的菌株均被鉴定到种,准确率为100%。结论 MADLI-TOF MS建立的马尔尼菲篮状菌自建库能够对于临床马尔尼菲篮状菌进行快速、准确的鉴定。     

31例艾滋病合并马尔尼菲篮状菌肺炎的临床特征

正马尔尼菲篮状菌病(PSM),是东南亚国家及我国南方地区艾滋病常见的机会性感染之一,但是,本病缺乏特征性临床表现、易与AIDS合并其他肺炎相混淆,诊断有一定难度。笔者对我院31例艾滋病合并马尔尼菲篮状菌肺炎患者的资料进行分析,现汇报如下。1资料与方法一般资料收集2012年1月至2017年12月在我院住院的31例确诊为艾滋病合并马尔尼菲篮状菌肺炎患者资料,除外合并其他细菌感染患者和分枝杆菌感染患者。其中,男性25例,女性6例,年龄24～71岁,平均43±10岁。     

定期转种法和低温冷冻法保藏致病真菌活性的能力比较

定期转种法和低温冷冻保存法是临床实验室最常用的两种真菌保存方法,为比较两种方法保藏致病真菌活性的能力,本研究使用两种保藏方法对实验室689株致病真菌保藏5年后进行检测。定期转种法是将菌落接种于马铃薯斜面培养基并将其储存在4℃冰箱,每6个月转种1次。低温冷冻法是挑取马铃薯斜面培养基上生长良好的菌落于无菌10%甘油中,放置在-80℃储存。保藏5年后,将两种方法保藏的菌株转种复苏,比较菌株的复活率。对于念珠菌属Candida、新生隐球菌Cryptococcus neoformans、毛癣菌属Trichophyton、曲霉属Aspergillus和孢子丝菌属Sporothirix真菌,两种方法的菌株复活率无统计学差异;对于小孢子菌属Microsporum真菌和马尔尼菲蓝状菌Talaromyces marneffei,使用低温冷冻法保藏的菌株复活率高于定期转种法保藏的菌株复活率;对于着色霉属Fonsecaea真菌,低温冷冻法保藏的菌株复活率低于定期转种法保藏的菌株复活率。因此,我们认为对于常见致病真菌的长期保藏,使用10%甘油作为保护剂的低温冷冻法优于定期转种法,但其不适用于着色霉属Fonsecaea真菌的长期保藏。     

大蜡螟医学真菌感染模型的研究现况

在研究真菌感染中建立合适的真菌感染动物模型非常重要,大蜡螟幼虫作为昆虫动物模型之一,相比于其他的动物模型具有多种技术优势,目前已被广泛用于新型隐球菌、小孢子菌、红色毛癣菌、念珠菌属、暗色真菌、马尔尼菲青霉菌、黄曲霉和烟曲霉等多种致病菌的毒力、发病机制、免疫学改变、抗菌药物的开发以及系统性真菌感染的治疗等各个研究领域。研究表明大蜡螟感染模型研究结果与哺乳动物的结果相似,因此可以用大蜡螟来替代哺乳动物进行相关研究,从而减少了实验对哺乳动物的依赖性。     

Seroprevalence of equine babesiosis in the Black Sea region of Turkey

The prevalence of Theileria equi and Babesia caballi was determined in equid blood samples in five provinces of the Black Sea region of Turkey by using the indirect fluorescent antibody test (IFAT). Of 153 samples, 53 (34.6%) and 33 (21.5%) were seropositive to B. caballi and T. equi, respectively. In addition, 8 (5.2%) of samples were seropositive to both T. equi and B. caballi. Anti T. equi and B. caballi antibodies were detected in all five regions. The prevalence of B. caballi was higher than T. equi in all counties. Antibodies to T. equi and B. caballi were detected in horses of all ages, and there were no significant differences among age groups. Out of 84 horses, 32 (38.0%) were positive for B. caballi infection and 20 (23.8%) were positive for T. equi infection. Five horses (5.6%) were found to be seropositive to both B. caballi and T. equi. Of 38 donkeys, 14 (36.8%) were found to be positive for B. caballi infection and 5 (13.1%) positive for T. equi infection. In addition, 2 (5.2%) samples were seropositive for both T. equi and B. caballi infections. Out of 31 mules, 8 (25.8%) were positive for B. caballi infection and 8 (25 8%) positive for T. equi infection. One (3.2%) sample was seropositive for both T. equi and B. caballi infections. Of all the animals in this study, only 3 horses were infected by Rhipicephalus turanicus and Hyalomma detritum, and no haemoparasites were detected by microscopic examination.     

Experimental American leishmaniasis and Chagas'' disease in the Brazilian squirrel monkey: cross immunity and electrocardiographic studies of monkeys infected with Leishmania braziliensis and Trypanosoma cruzi

, and 1988. Experimental American leishmaniasis and Chagas' disease in the Brazilian squirrel monkey: cross immunity and electrocardiographic studies of monkeys infected with Leishmania braziliensis and Trypanosoma cruzi. International Journal for Parasitology 18: 1053–1059. Adult, laboratory-bred squirrel monkeys (Saimiri sciureus) previously infected with either Leishmania braziliensis braziliensis or L. b. panamensis were challenge infected with blood-form trypomastigotes of Trypanosoma cruzi (Brazil strain). Monkeys previously infected with T. cruzi were challenged with stationary phase promastigote forms of L. b. braziliensis. Monkeys were examined during the course of challenge for evidence of infection, electrocardiographic alterations and parasite-specific antibody responses. T. cruzi epimastigotes were cultured from the blood of monkeys up to 3 months after challenge with this parasite. Unulcerated cutaneous lesions appeared and persisted in monkeys challenged with L. b. braziliensis. The formation of satellite lesions was observed in one monkey. Increased QRS intervals were not observed in T. cruzi challenged monkeys without prior cardiac irregularities and QRS left axis shifts were observed in only two of these monkeys. Elevated titers of parasite binding IgM and IgG specific for both T. cruzi and L. braziliensis were observed in all monkeys following challenge. These results indicate that prior infection with T. cruzi or L. braziliensis does not protect against heterologous challenge infection with these organisms. However, prior infection with Leishmania parasites may provide some protection against chagasic cardiopathies.     

Synergism and antagonism between two trematode species in the snail Lymnaea rubiginosa

Synergism and antagonism between two trematode species in the snail Lymnaea rubiginosa. Internationaljournal for Parasitology 3: 729–733. Sporocysts of Trichobilharzia brevis in the snail exerted a synergistic effect on sporocysts of Echinostoma hystricosum: The rate of infection with E. hystricosum was much higher in snails harboring T. brevis than in control snails with no other infection. Rediae of E. hystricosum and sporocysts of T. brevis were antagonistic, the predatory rediae consuming the sporocysts and ultimately eliminating T. brevis from the snail. Once a snail was occupied by E. hystricosum it could not be superinfected by T. brevis.     

Persistence of acquired immunity to Trichostrongylus colubriformis in sheep after termination of infection

Lambs were infected with 6000 Trichostrongylus colubriformis L3 per week for 18, 12 or 6 weeks, beginning at ages 14, 20 and 26 weeks, respectively. At the end of the primary infection subgroups had geometric mean adult worm burdens of 5000, 15,000 and 18,000, respectively. In the remaining sheep the worm population was removed with anthelmintic, and sheep had no further larval intake until challenged with T. colubriformis 1,6, 12, 18 or 24 weeks later. In the groups given 18 or 12 weeks primary infection, establishment of challenge doses was low (less than 25% of establishment in helminth naive controls) in most animals at all challenge times. However, for the groups given 6 weeks primary infection, establishment was low only at the first two challenge times. Thereafter it had similar mean to control groups, but much greater variance. Other subgroups were challenged with T. colubriformis, Ostertagia circumcincta and Haemonchus contortus 1 week after worm removal. In these animals T. colubriformis establishment was not different to animals challenged at the same time with T. colubriformis alone, however immunity to T. colubriformis afforded little protection against the other species. The results of this experiment were incorporated into a simulation model of the population dynamics of T. colubriformis.     

Trypanosoma cruzi infection by oral route: how the interplay between parasite and host components modulates infectivity

Trypanosoma cruzi infection by oral route constitutes the most important mode of transmission in some geographical regions, as illustrated by reports on microepidemics and outbreaks of acute Chagas' disease acquired by ingestion of food contaminated with parasites from triatomine insects. In the mouse model, T. cruzi metacyclic trypomastigotes invade the gastric mucosal epithelium, a unique portal of entry for systemic infection. High efficiency of metacyclic forms in establishing infection by oral route is associated with expression of gp82, a stage-specific surface molecule that binds to gastric mucin and to epithelial cells. Gp82 promotes parasite entry by triggering the signaling cascades leading to intracellular Ca²⁺ mobilization. T. cruzi strains deficient in gp82 can effectively invade cells in vitro, by engaging the Ca²⁺ signal-inducing surface glycoprotein gp30. However, they are poorly infective in mice by oral route because gp30 has low affinity for gastric mucin. Metacyclic forms also express gp90, a stage-specific surface glycoprotein that binds to host cells and acts as a negative regulator of invasion. T. cruzi strains expressing gp90 at high levels, in addition to gp82 and gp30, are all poor cell invaders in vitro. Notwithstanding, their infectivity by oral route may vary because, unlike gp82 and gp30, which resist degradation by pepsin in the gastric milieu, the gp90 isoforms of different strains have varying susceptibility to peptic digestion. For instance, in a T. cruzi isolate, derived from an acute case of Chagas' disease acquired by oral route, gp90 is extensively degraded by gastric juice in the mouse stomach and this renders the parasite highly invasive towards target cells. If such an exacerbation of infectivity occurs in humans, it may be responsible for the severity of the disease reported in outbreaks of oral infection.     

The interaction of Trypanosoma congolense and Haemonchus contortus in Djallonké sheep

The interaction between Trypanosoma congolense and Haemonchus contortus was studied in 5 groups of 8 Djallonké sheep. Two groups received a single infection with either H. contortus or T. congolense, and 2 groups were infected with T. congolense followed by H. contortus (TH) or vice versa (HT). One group was kept as uninfected controls. Mortality due to infection was observed only in the dual infection groups. In the TH group, the effects were more acute whereas in the HT group they were more chronic. No significant differences in weight gain could be demonstrated between infected and control groups. Djallonké sheep are able to withstand a single infection with either T. congolense or H. contortus, which confirms their trypanotolerant nature and provides preliminary indication of resistance against helminth infections. However, when exposed to successive infections with both parasites, some of the animals lose this tolerance.     

Differential detection of Hammondia hammondi from Toxoplasma gondii using polymerase chain reaction

Hammondia hammondi and Toxoplasma gondii are two related coccidian parasites, with cats as definitive hosts and warm-blooded animals as intermediate hosts. It is difficult to differentiate them by morphological and serological parameters. In the present study, primers were designed to specifically amplify the ITS-1 region of H. hammondi to differentiate it from T. gondii. Attempts were made to detect the presence of H. hammondi DNA in the tissues of mice infected with H. hammondi alone, as well as from mixed infections with T. gondii, using the newly designed primers. The de novo primers effectively amplified the H. hammondi-specific target fragment from all samples containing H. hammondi, including those with concomitant T. gondii infection. Further, the primers did not amplify any fragment from the related parasites like T. gondii, Neospora caninum and Hammondia heydorni. The new primers provide simple and efficient means to differentially diagnose H. hammondi from T. gondii even in samples containing both parasites, thus obviating the need for other labourious techniques like mouse bioassay and in vitro cultivation.     

High levels of congenital transmission of Toxoplasma gondii in a commercial sheep flock.

Our current understanding of congenital transmission of Toxoplasma gondii from ewe to lamb dictates that infection frequently results in abortion and the death of the developing foetus, that the birth of live infected lambs occurs rarely and that the cat is the predominant source of infection in ewes. Using direct polymerase chain reaction detection of T. gondii, we report high levels of congenital transmission occurring in a commercially managed sheep flock. We sampled foetal-derived placental tissue and tissues from aborted lambs and showed that congenital transmission was detected in these tissues from 61% of all pregnancies. Where pregnancies resulted in the death of one or more lambs, T. gondii was detected in the lamb tissue for all but one of 18 (94%) pregnancies. Of the successful pregnancies resulting in the birth of live lambs we were able to detect T. gondii in foetal-derived placental tissue from 37 of 70 (42%) pregnancies. These results show that congenital transmission is occurring in a high percentage of lambings including normal healthy lambings, at this farm, suggesting that this route of transmission from generation to generation may be much more significant than that reported previously. These results may have implications for sheep husbandry and future epidemiological studies of T. gondii.