间日疟、恶性疟混合感染1例治疗报告

2009年龙岩市报告1例间日疟、恶性疟混合感染病例,患者在国外感染、发病,曾接受过治疗,回国后再次发病。在国内经3个疗程青蒿琥酯(1 800 mg)和4个疗程的氯伯8 d疗法(氯喹4 800 mg、伯氨喹720 mg)治疗后痊愈。     

Plasmodium simium and Saimiri boliviensis as a model system for testing candidate vaccines against Plasmodium vivax

Observations on Plasmodium simium infections in Saimiri boliviensis boliviensis monkeys suggest that this host-parasite combination would be a suitable model for the testing of candidate vaccines against Plasmodium vivax. To evaluate the normal course of infections, parasitemia in 52 splenectomized S. boliviensis boliviensis monkeys infected with P. simium were analyzed. The mean maximum parasite count for 31 monkeys after injection with trophozoite-infected erythrocytes was 77,580/microL. Twenty-one monkeys were infected via sporozoites, and prepatent periods ranged from 14 to 24 days with a median of 15 days. The mean maximum parasite count was 29,234/microL. The mean maximum parasite count for monkeys previously infected with Old World P. vivax was 26,337/microL versus 56,362/microL for those previously infected with New World P. vivax, possibly suggesting a closer antigenic relationship between P. simium and the Old World parasites.     

Antimalarial activity of a riboflavin analog against Plasmodium vinckei in vivo and Plasmodium falciparum in vitro

The riboflavin analog 10-(4'-chlorophenyl)-3-methylflavin was found to have significant activity against Plasmodium vinckei vinckei when administered orally and parenterally; it was active against P. falciparum in culture. It inhibited mouse erythrocyte glutathione reductase in a dose-dependent manner. When administered orally, 5-deazariboflavin was not active in vivo although it has been shown to have activity against P. falciparum in vitro.     

Identification of a polymorphic Plasmodium vivax microsatellite marker

Microsatellite markers derived from simple sequence repeats have been useful in studying a number of human pathogens, including the human malaria parasite Plasmodium falciparum. Genetic markers for P. vivax would likewise help elucidate the genetics and population characteristics of this other important human malaria parasite. We have identified a locus in a P. vivax telomeric clone that contains simple sequence repeats. Primers were designed to amplify this region using a two-step semi-nested polymerase chain reaction protocol. The primers did not amplify template obtained from non-infected individuals, nor DNA from primates infected with the other human malaria parasites (P. ovale, P. malariae, or P. falciparum). The marker was polymorphic in P. vivax-infected field isolates obtained from Papua New Guinea, Indonesia and Guyana. This microsatellite marker may be useful in genetic and epidemiologic studies of P. vivax malaria.     

Plasmodium malariae infection boosts Plasmodium falciparum gametocyte production

We analyzed records of malaria therapy patients sequentially or simultaneously inoculated with Plasmodium falciparum and Plasmodium malariae. Gametocyte production was enhanced in P. falciparum by prior or concurrent P. malariae infection but diminished or unaffected in P. malariae by P. falciparum. Conversely, asexual-form production was diminished in P. malariae but unaffected in P. falciparum.     

三日疟与恶性疟混合感染一例报告

患者．男性，36岁，四川省射洪县人。2004年11月中旬到云南，在瑞丽中缅两国边境接壤的秀岛镇做运输木材工作。弄岛三面被缅甸环绕，距瑞丽市28km。患者从边境多次往返于缅甸境内运木材．每次停留约1周。于2005年3月底返乡后有过感冒样前驱症状：表现为周身不适、头晕、乏力、腰酸背痛、食欲不振伴有轻微呕吐，并于4月5日起反复发热，4月9日后表现为不规则发热并日渐加重．体温最高达40．4℃，伴有寒战、呕吐、头痛、咳嗽。     

Transmission of mixed Plasmodium species and Plasmodium falciparum genotypes

We studied malaria transmission by comparing parasite populations in humans and mosquito vectors at the household level. Blood samples were collected from all inhabitants for microscopic detection of gametocytes and polymerase chain reaction analysis. The next morning, blood-fed resting mosquitoes were collected inside the bed nets used by the individuals surveyed the previous afternoon. After 8 days of maintenance, mosquitoes were dissected, and midguts and salivary glands were recovered for polymerase chain reaction analysis. Results showed that parasite distribution was the same in the 2 hosts when compared at each household but was different when whole populations were analyzed. Different associations of Plasmodium species seem to occur in humans (Plasmodium falciparum/Plasmodium malariae) and mosquitoes (P. falciparum/Plasmodium ovale). Regarding P. falciparum infections, a higher proportion of single-genotype infections and less allele diversity are observed in mosquitoes than in humans.     

16alpha-bromoepiandrosterone, a dehydroepiandrosterone (DHEA) analogue, inhibits Plasmodium falciparum and Plasmodium berghei growth.

Dehydroepiandrosterone (DHEA) and its analogue, 16alpha-bromoepiandrosterone (alpha-epi-Br), may have activity against viral and parasitic infections, including human immunodeficiency virus (HIV) and Cryptosporidium parvum. Therefore, we evaluated its antimalarial effects on Plasmodium falciparum and Plasmodium berghei. In vitro, chloroquine (CQ)-sensitive and resistant strains of P. falciparum parasitized red blood cells were incubated with escalating doses of alpha-epi-Br or CQ. In vivo, 62 rats were infected with P. berghei and treated with CQ or alpha-epi-Br. At the highest doses tested against a CQ-sensitive strain, parasitemias decreased from 25.4% in the saline control group to 4.3% and 4.8% in the alpha-epi-Br and CQ groups, respectively (P < 0.05). Against two CQ-resistant strains, parasitemias decreased from 22.3-28.8% and 24.8-30% in the CQ and saline groups, respectively, to 2.5-2.7% in the alpha-epi-Br groups (P = 0.003). In vivo, on Day 4, parasitemias decreased from 23% in the saline group to 9-12% and 12% in the in alpha-epi-Br and CQ groups, respectively (P < 0.05). These data demonstrate that alpha-epi-Br shows activity against CQ-sensitive and resistant strains of P. falciparum in vitro. At the doses tested against P. berghei in vivo in rats, alpha-epi-Br is comparable to CQ.     

多重PCR种特异性检测恶性疟原虫和间日疟原虫方法的建立

目的建立恶性疟原虫和间日疟原虫种特异性检测的多蕈PCR方法,用于疟疾的检测和诊断.方法根据疟原虫18S核糖体小亚基ssRNA的基因序列设计合成8对11条引物,通过对恶性疟、间日疟患者及健康对照者血样的DNA进行扩增,选择出敏感性和特异性最佳的引物用于建立多重PCR方法,并用梯度变化的方法分别对引物浓度、复性温度、延伸温度和循环次数等反应参数进行比较分析,优化PCR反应条件.利用优化后的多重PCR埘采自云南和上海的139份疟疾患者血样和32份非疟疾患者血样进行检测,以镜检方法为金标准,分析多重PCR方法检测患者血样的敏感性和特异性.结果从8对11条引物中优选出2对共3条引物用于建立多重PCR.利用这3条引物进行多重PCR,一次反应即可完成对恶性疟原虫和间日疟原虫的种特异性鉴定.对疟疾和非疟疾患者血样检测结果显示,该方法检测患者血样的敏感性为97.8%,特异性为100%.结论多重PCR方法敏感、特异、可进行批量检测,适用于对人群的疟疾监测和疑似疟疾病例的诊断,并能鉴定恶性疟原虫和间日疟原虫虫种.     

Characterization of a UBC13 kinase in Plasmodium falciparum

Protein kinases are generally recognized as attractive drug targets to treat a variety of human diseases. Recent analysis of the Plasmodium falciparum kinome identified several kinases that are entirely unique to Plasmodium species. The specific functions and targets of most of these enzymes remain largely unknown. Here, we have identified a P. falciparum kinase (PfPK9/PF13_0085 ORF) that does not cluster with any of the typical eukaryotic protein kinases. PfPK9 protein expression was induced approximately 18 h after red blood cell infection, and was mainly localized to the parasitophorous vacuolar membrane as well as the cytosol. Recombinant PfPK9 autophosphorylated in vitro and specifically phosphorylated the exogenous substrate histone H1, indicating that it is catalytically active. Phosphopeptide mapping studies showed that autophosphorylation occurred at three residues: T082, T265, and T269. We identified a P. falciparum homolog of the E2 ubiquitin-conjugating enzyme 13 (UBC13) as an endogenous substrate for PfPK9. PfPK9 phosphorylated UBC13 at S106, a highly conserved residue among eukaryotic E2s, and suppressed its ubiquitin-conjugating activity. Our findings not only describe a previously uncharacterized Plasmodium kinase and its likely in vivo target, but also suggest that modulation of UBC13 activity by phosphorylation may be a common regulatory mechanism in eukaryotes.     

Plasmodium knowlesi in a traveller returning to New Zealand

The recent discovery that Plasmodium knowlesi causes malaria in human populations, established it as the fifth species of plasmodium that may do so. A case of P. knowlesi malaria is described in a helicopter pilot from New Zealand, who became ill after returning from recurring visits to Malaysian Borneo in June 2010. His P. knowlesi infection was not detected using microscopic examination and a rapid diagnostic test for malaria, but was confirmed by both PCR (polymerase chain reaction) and sequence analysis showing homology with the ribosomal RNA gene for P. knowlesi. He responded rapidly to treatment with artemether & lumefantrine combination. The evolution of a rapid diagnostic kit to diagnose P. knowlesi is needed, for early identification and appropriate anti-malarial therapy of suspect cases are both critical in the prevention of the potentially life-threatening disease through P. knowlesi. Clinicians need to consider knowlesi infection in the differential diagnosis in recent-onset febrile travellers to areas of forestation in Southeast Asia.     

Characterization of a Plasmodium falciparum macrophage-migration inhibitory factor homologue

BACKGROUND: Macrophage-migration inhibitory factor (MIF), one of the first cytokines described, has a broad range of proinflammatory properties. The genome sequencing project of Plasmodium falciparum identified a parasite homologue of MIF. The protein is expressed during the asexual blood stages of the parasite life cycle that cause malarial disease. The identification of a parasite homologue of MIF raised the question of whether it affects monocyte function in a manner similar to its human counterpart. METHODS: Recombinant P. falciparum MIF (PfMIF) was generated and used in vitro to assess its influence on monocyte function. Antibodies generated against PfMIF were used to determine the expression profile and localization of the protein in blood-stage parasites. Antibody responses to PfMIF were determined in Kenyan children with acute malaria and in control subjects. RESULTS: PfMIF protein was expressed in asexual blood-stage parasites, localized to the Maurer's cleft. In vitro treatment of monocytes with PfMIF inhibited random migration and reduced the surface expression of Toll-like receptor (TLR) 2, TLR4, and CD86. CONCLUSIONS: These results indicate that PfMIF is released during blood-stage malaria and potentially modulates the function of monocytes during acute P. falciparum infection.     

Plasmodium falciparum infection in a 8-year old boy

A 8-year old Japanese boy who returned from Tanzania was admitted to our hospital because of fever, vomiting, and headache. He was diagnosed as a Plasmodium falciparum infection verified by a blood smear. He was treated with quinine and halofantrine, and recovered completely. Malaria infection should be considered when patients return from Malaria endemic areas.     

Role of macrophage-processed antigen in a Plasmodium berghei model

Summary The present study demonstrates that malarial parasite could be processed by macrophages in vitro to release 'super antigens'. These super antigens obtained from the peritoneal macrophages were more protective than those processed by the splenic adherent cells. BCG-stimulated macrophages were also able to process the antigens efficiently and these antigens were even superior to those obtained from the unstimulated macrophages. These modified antigens were potent inducers of DFPS to malarial antigens. It is thus concluded that parasite antigens, processed in vitro, carry specific immunogenic potential and are able to protect the recipients to parasite challenge.     

Detection of Plasmodium falciparum using a synthetic DNA probe

A labeled synthetic polynucleotide representing a repetitive sequence from Plasmodium falciparum was hybridized with genomic DNA spotted on nitrocellulose. After an overnight exposure, 0.1 ng of P. falciparum DNA was specifically detected and 0.01 ng was detected after an exposure of 1 week. The synthetic probe showed no cross-hybridization with host DNA or with DNA isolated from other species in the phylum Apicomplexa, P. vivax and Babesia species. Since synthetic DNA is easily prepared, the observed sensitivity and specificity suggests that synthetic DNA probes would be generally useful in diagnosis.