方光焘：被遮蔽的新文学作家

作为中国当代语言学家的方光焘,被誉为南派语言学的杰出代表;然而作为新文学作家的方光焘,却鲜为人知。方光焘早年曾积极投身新文学运动,是《创造社》最早的一批社员之一。他不仅亲身实践创作了小说,撰写了多篇文学评论,还翻译推介了大量的日英法等国著名作家的文学作品,合作编译了《文学入门》等理论书籍;他从理论与实际等多方面,支持并推动了中国新文学的发展。从某种程度而言,对方光焘文学创作的梳理与总结,也是对新文学第一代作家的一次学理性追踪。

Selective Effect of Qinghaosu on Different Stages of Plasmodium falciparum in Vitro

Using highly synchronous cultures of Plasmodium falciparum in vitro,the susceptibi- lity of the different stages of the intraerythrocytic parasites to Qinghaosu (QHS) was assessed.The anti- parasitic effect of QHS was measured by comparing the changes of irradiation of^3 H-hypoxanthine in- corporated into the nucleic acids of parasites exposed to various concentrations of QHS at different stages of growth.It was found that the trophozoite stage of the parasite was the most sensitive to QHS, whereas the early ring stage was the least sensitive,and the sensitivities of the late ring and schizont stages fell between those of the early ring and trophozoite stages.The results revealed the correlation of stage-dependent effects of QHS with the blockade of the protein metabolism of the parasite.

Oral vaccination of mice against rodent malaria with recombinant Lactococcus lactis expressing MSP-1_(19)

AIM： To construct the recombinant Lactococcus/actis as oral delivery vaccination against malaria. METHODS： The C-terminal 19-ku fragments of MSP1 （MSP-119） of Plasmodium yoelii265-BY was expressed in L. lactis and the recombinant L. lact/s was administered orally to BALB/c and C57BL/6 mice. After seven interval vaccinations within 4 wk, the mice were challenged with P. yoelii 265-BY parasites of erythroo/tic stage. The protective efficacy of recombinant L. lactiswas evaluated. RESULTS： The peak parasitemias in average for the experiment groups of BALB/c and C57BL/6 mice were 0.8± 0.4% and 20.8±26.5%, respectively, and those of their control groups were 12.0±0.8% and 60.8±9.6%, respectively. None of the BALB/c mice in both experimental group and control group died during the experiment. However, all the C57BL/6 mice in the control group died within 23 d and all the vaccinated mice survived well. CONCLUSION： The results imply the potential of recombinant L. lactis as oral delivery vaccination against malaria.

Non-traumatic splenic rupture:Report of seven cases and review of the literature

AIM： TO evaluate seven patients with non-traumatic splenic rupture （NSR）. NSR is an uncommon dramatic abdominal emergency that requires immediate diagnosis and prompt surgical treatment to ensure the patient＇s survival. METHODS： Within 11 years, seven cases were evaluated for patient characteristics, anamnesis and symptoms, method of diagnosis, findings of laparotomy, and etiology of NSR. RESULTS： There were six （86%） male and one female （14%） patient, whose mean age was 36 ± 12.8 （17-56） years. We report here four cases of Plasmodium vivax malaria （cases Ⅰ-Ⅳ）, one case of hemodialysis （case Ⅴ）, one case of spontaneous splenic rupture （case Ⅵ）, and one case of hairy cell leukemia （case Ⅶ）. Splenectomy was performed in all patients. All of them made an uneventful recovery and were discharged in stable condition. CONCLUSION： NSR is a rare entity that needs a high index of suspicion for diagnosis. Using ultrasonography or computer tomography, and peritoneal aspiration of fresh blood may assist in the diagnosis of NSR. Increased awareness of NSR can enhance early diagnosis and effective treatment.

Influence of Weather and Climate on Malaria Occurrence Based on Human-Biometeorological Methods in Ondo State, Nigeria

This study focuses on the influence of weather and climate on malaria occurrence based on human-biometeorological methods was carried out in Ondo State, Nigeria using meteorological and malaria dataset in the state for the period from 1998 to 2008. In addition, sea surface temperatures （SSTs） over equatorial Pacific Ocean were integrated in the analysis. The association between each of the meteorological-biometeorological parameters and clinical-reported malaria cases was examined by using Poisson distribution and log as link function between the two categories of dataset. The next step was the building of a model by using Poisson multiple regression models （GLMs） in order to know the weather variables that lead to statistically changes in clinical-reported malaria cases. The study revealed that an increase of I m.s1 of wind speed can lead to an increase of about 164% and 171% in the monthly occurrence of malaria at 95% confidence interval in derived savanna and humid forest zone respectively. Also, an increase of I ℃ in air temperature and sea surface temperature is associated with 53.4% and 29% increase in monthly malaria occurrence （CI： 95%） in derived savanna while an increase of 1 ℃ in air temperature and sea surface temperature is associated with 56.4% and 15.4% increase in monthly malaria occurrence at 95% confidence interval in humid forest zone of Ondo State

The Control of Malaria among PLWHA in Calabar, Cross River State, Nigeria

The purpose of the study was to examine RBM programme＇s efforts at controlling malaria among PLWHA and explore their perception of the control strategies. The study was a descriptive survey involving guided interviews of top managers of Roll Back Malaria （RBM） programme. A structured questionnaire was administered to 108 PLWHA attending an HIV/AIDS clinic in a secondary health facility in Calabar. Data were analyzed using descriptive statistics. Thematic analysis revealed that RBM programme strategies include effective case management, promotion of Long Lasting Insecticide Treated Nets （LLINs）, intermittent preventive treatment （IPT） and integrated vector management （IVM）. Complementary results showed that 104 （92%） admitted accessibility to malarial treatment. Although 83 （57.7%） of PLWHA have LLINs, only 63 （42.3%） use them. Majority of the respondents 89 （60%） have not heard of indoor/outdoor residual spraying （IRS）. How to get IRS services and lack of money to buy it were listed as a barrier to its use. Malarial treatment was accessible to PLWHA. The barriers to the use of ITN and IRS could be addressed through free distribution of odorless ITN and IRS to PLWHA. Higher rates of utilization of the products can be achieved through behavioural change communication.

Toll-like receptors,a double-edged sword in immunity to malaria

Toll-like receptors(TLRs) are a central component of innate immune system and play a major role as the initiator of the innate immune responses to defend against bacteria,viruses,parasite and other pathogens.During malaria infection,TLRs signaling pathways are initialed with the recognition of Plasmodium glycosylphosphatidylinositols(GPI) and hemozoin as pathogen-associated molecular patterns(PAMPs).And then,activation of TLRs signaling induces specific biological responses against malaria parasites invasion.However,TLRs are also involved in malaria pathogenesis and enhancement of immune tolerance and evasion for malaria infection.Moreover,malaria parasites regulate selectively TLRs expression on immune cells.Thus,these evidences indicated that TLRs have contrary roles on malaria infection.Understanding the complicated roles of TLRs on malaria infection will contribute us to design more effective anti-malaria drugs or vaccines.

ENDOGENOUS EXPRESSION AND HLA STABILIZATION ASSAY OF PLASMODIUM FALCIPARUM CTL EPITOPE MINIGENE IN HUMAN HLA- A2.1 AND HLA- B51 CELLS

To evaluate the Plasmodium falciparum CTL epitope vaccines in HLA class I allele specific human cell lines that have high frequency among Chinese population. Methods. Synthesized oligonucleotides encoding for P.f. CTL epitope genes, constructed eukaryotic expression plasmids, transfected the minigenes into HLA class I allele specific human cell lines and identified endogenous expressing of the minigenes by RT- PCR and HLA stabilization assay. Results. Two mini- genes encoding Plasmodium falciparum CTL epitopes were designed and cloned, respectively, into an eukaryotic expressing vector to form TR26 which was restricted to HLA- B51, SH6 which was restricted to HLA- A2.1, and TS, which had the two aforementioned mini- genes fused in tandem. All of these CTL epitope genes were transfected and endogenously expressed in respective cell lines containing appropriate HLA molecules. The obviously increased expressions of HLA class I molecules were detected in the transfected cell lines. It was demonstrated that the two discrete Plasmodium falciparum epitope genes were effectively processed and presented, and the close proximity of the two epitope genes in one chain as in mini- gene TS did not interfere with the processing and presenting of each epitope gene in corresponding cell line. Conclusion. A successful expression and presentation of multiple CTL epitope mini- gene in MHC class I allele specific human cell lines were demonstrated by an in vitro assay, which could be corresponding to the vaccination of CTL vaccines in people with different MHC I molecules. This work also suggested the possibility of constructing a multiple CTL epitope plasmodium falciparum DNA vaccine that could cover most of Chinese population.

Assessment of HRP2-Based RDT in Diagnosing Malaria Cases

Background： HRP2-based Rapid Diagnostic Tests （RDTs） for malaria ensure a rational use of artemisinin-based combination therapy （ACT）. The HRP2 antigen can go through the cerebrospinal fluid （CSF）. Purpose： To assess the HRP2-based RDT in malaria and detect the HRP2 in CSF. Methods： From November 2006 to May 2007, all patients under 15 years showing clinical symptoms of malaria were included. RDT was performed on the CSF and peripheral blood. Results： Out of the 951 patients included, 131 （13.7%） were confirmed through RDT and 130 （13.6%） through thick blood smear. Sensitivity and specificity stood at 96.96% and 99.71% respectively, for uncomplicated cases and at 100% and 99.13% for severe cases. Tests to detect HRP2 in the CSF of 52 cases were negative. Conclusion： Tests to detect HRP2 in the CSF could make it possible to diagnose severe malaria cases when peripheral parasitemia would be below the detection threshold.

Attitudes and Practices of Health Care Providers Regarding the Management of Uncomplicated Malaria in Abidjan, Cote d＇lvoire

Malaria is a major public health problem in the Cote d＇Ivoire where it is the leading cause of morbidity and mortality. The objective of this study was to assess the knowledge, attitudes and practices of health care providers on the diagnosis and therapeutic procedures used to ensure the management of uncomplicated malaria in the health district of Abidjan. A cross-sectional study was conducted from November 2008 to December 2008 among 169 caregivers who treated 1,691 cases of uncomplicated malaria. Results： The knowledge of the caregivers of the national guidelines regarding malaria was sufficient （89%）. A diagnosis of uncomplicated malaria was established only on clinical arguments （70%）. The percentage of patients who were prescribed artemisinin-based combination therapy （ACT） was 86%. However, 25% of the antimalarials drugs that were prescribed to patients （oral quinine, artemisinin derivatives monotherapy, and herbal medicine） did not meet the recommendations on first choice treatment as suggested by the national program against malaria. These results indicate sufficient knowledge of the national guidelines for the treatment of malaria by health care providers as evidenced by acceptable prescriptions for ACTs despite an incomplete knowledge of the guidelines.

Submicroscopic Plasmodial Infection May Lead to Severe Malaria in Children

Malaria is one of the leading causes of consultation in African pediatric hospitals. In Gabon, malaria transmission is perennial. Plasmodium falciparum, responsible for the most severe form of the disease, represents more than 95% of all species. In P. falciparum infection, the hyperparasitemia accounts among the main criteria of disease severity. However, in many endemic countries, a significant decrease of malaria burden accompanying with the diminution of parasite load in infected individuals has been demonstrated. The objective of the study was to analyze the occurrence of febrile syndrome in childhood and investigate whether the acute febrile illness could be associated with P. falciparum submicroscopic infection. A cross-sectional study was carried out during January to March 2013 in Franceville. A total of 203 acute febrile children were enrolled. A clinical examination and biomedical analysis including parasitological diagnosis by microscope were carried out in all the patients and PCR on microscope negative ones. Of 203 children recruited for febrile syndrome, 111 have been diagnosed positive for P. falciparum infection, 73 （35.9%） by microscope （ME） and 38 （18.71%） by PCR （submicroscopic infection = SM1） with an overall prevalence of 54.68%. Of the 11 1 P. falciparum infected individuals and according to the WHO criteria, 35 （31.53%） children showed a clinical picture of severe malaria against 76 （68.47%） others classified as uncomplicated malaria. The overall prevalence rates were therefore estimated as 17.24 （35/203） for severe cases and 37.43% （76/203） for uncomplicated ones. Clinically, these severe malaria cases （27 ME＋ and 8 PCR＋） were mainly composed of 85.71% of anaemic patients （30/35）, 71.14% of prostrated individuals （25/35） and 57.14% of children with clinical icterus （20/35）. However, only two cases of severe anaemia were observed, the remaining others cases were moderate （10） and mild anaemia （18）. More interestingly, eight submicroscopic infected patients （22.85%） were found with neurological manifestations （prostration） and all were experiencing thrombocytopenia. Lastly, 1 hyperparasitemia, 6 hypoglycemia and 2 respiratory distresses were also observed among these severe malaria cases. P. falciparum submicroscopic infection may lead to severe malaria in perennial transmission area.

Malaria： Autophagy as a Potential Therapeutic Target

Abstract： Malaria, where the causative agent Plasmodium is rapidly gaining resistance to practically all the antimalarial drugs in clinical use, requires the identification of new drug targets to enable the discovery of novel, more effective and safer drugs to treat the disease. Advancements in molecular techniques have provided the proof of existence of autophagy in Plasmodium; however, its role（s） in malaria is only becoming to be understood. Nevertheless, some of the recently explored dimensions of autophagy in Plasmodium have indicated its fairly larger role in parasite survival and growth. But then, autophagy is also essential for host cell survival and defence. There is thus need to explore chemotherapeutic strategies to specifically target autophagy in both the parasite and host. This review focuses on autophagy pathways in Plasmodium and in host with a view to identify autophagy-related new drug targets for the discovery of novel antimalarial drugs.

Reliability of Rapid Diagnostic Test （RDT） for Malaria among Pregnant Women in Ido-Ekiti, Western Nigeria

Background： Malaria is the commonest cause of anemia in pregnancy with severe consequence on the developing fetus. Recent clamor by the WHO for testing before treatment has driven a need to assess the effectiveness of available Rapid Diagnostic Tests （RDTs）. Objective： To determine the reliability of Rapid Diagnostic Tests （RDTs） for malaria among pregnant women booking in Federal Teaching Hospital, Ido-Ekiti, Nigeria. Materials and Methods： A cross-sectional study of 240 pregnant women were recruited at booking over a period of twenty weeks. A semi-structured questionnaire sought information about socio demographic data. Blood samples were taken for malaria and diagnosis was done using RDT and Microscopy. Results： Prevalence of malaria was 22.1% by microscopy and 27.5% by RDT. The sensitivity of RDT was 88.7% and specificity was 89.8%. The positive predictive value （PPV） of RDT was 71.2%, the Negative predictive value （NPV） of RDT was 96.6% and accuracy was 89.6%. The reliability of RDT was good （Kappa statistics = 0.731）. The reliability of RDTs when compared with that of Microscopy was also good （Kappa statistics = 0.722）. Conclusions： RDTs was an effective screening test for malaria among the respondents. Hence, primary care physician should utilize this resource by advocating for its availability.

Effect of Plasmodium yoelii YM Infection on Vaccination with 19 kDa Carboxylterminus of the Merozoite Surface Protein 1 (MSP1_(19))

We have previously demonstrated the ability of malaria parasites to interfere with specific immune responses. CD4 T cells specific to parasite antigens, but not CD4 T cells specific to an irrelevant antigen, ovalbumin (OVA), are de- leted via apoptosis during malaria infection. It is of interest, therefore, to investigate the immune responses that developed following vaccination with the 19 kDa carboxylterminus of the merozoite surface protein 1 (MSP119) in mice that had previ- ously experienced malaria infection. In this study, pre-exposure of mice to Plasmodium yoelii elicited native anti-MSP119 an- tibody responses, which could be boosted by vaccination with recombinant MSP119 . likewise, infection of MSP119-primed mice with Plasmodium yoelii ( P . yoelii) led to an increase of anti-MSP119 antibodies. MSP119 vaccination of malaria pre- exposed mice or immunization by infection/cure of MSP119-primed mice enabled the mice to survive challenge infection, with the former group having slightly lower parasitaemia. The data suggest that exposure to malaria infection primes a natural im- mune response which can be boosted by vaccination. This information is relevant to the development of a vaccine for use in individuals living in malaria-endemic areas.

Efficacy of dihydroartemisinin-mefloquine on acute uncomplicated falciparum malaria

Objective To evaluate the clinical efficacy of dihydroartemisinin-mefloquine on acute uncomplicated falciparum malaria. Methods Fifty-four patients with symptomatic falciparum malaria were allocated to receive oral dihydroartemisinin at a single dose of 120?mg on day 1, followed by mefloquine, 750?mg and 500?mg on days 2 and 3, respectively. Follow-up was performed on days 1,2,3,4,7,14,21, and 28. Results All patients had a rapid initial response to treatment. The parasite clearance time (PCT) after treatment was 30.7±3.6 hours. The fever subsidence time (FST) after treatment was 21.2±2.8 hours. Two patients had a recrudescence 21 and 25 days respectively after the disappearance of parasitemia, hence the recrudescence rate was 3.7% and the cure rate was 96.3%. No serious adverse effects were observed, only mild and transient nausea, vomiting and loss of appetite. Conclusion A combination of dihydroartemisinin and mefloquine is effective in the treatment of acute uncomplicated falciparum malaria.

The backward bifurcation of a model for malaria infection

In this paper, an epidemic model of a vector-borne disease, namely, malaria, is consi- dered. The explicit expression of the basic reproduction number is obtained, the local and global asymptotical stability of the disease-free equilibrium is proved under certain conditions. It is shown that the model exhibits the phenomenon of backward bifurcation where the stable disease-free equilibrium coexists with a stable endemic equilibrium. Further, it is proved that the unique endemic equilibrium is globally asymptotically stable under certain conditions.

Optimal control of intervention strategies in malaria-tuberculosis co-infection with relapse

A model which incorporates some of the basic epidemiological features of the co- dynamics of malaria and tuberculosis （TB） is formulated and the effectiveness of current intervention strategies of these two diseases is analyzed. The malaria-only and TB-only models are considered first. Global stability disease-free steady states of the two sub- models does not hold due to the co-existence of stable disease-free with stable endemic equilibria, a phenomenon known as backward bifurcation. The dynamics of the dual malari^TB model with intervention strategies are also analyzed. Numerical simulations of the malaria-TB model are carried out to determine whether the two diseases can co- exist. Lastly, sensitivity analysis on key parameters that drive the disease dynamics is performed in order to identify their relative importance to disease transmission.

Threshold conditions for a family of epidemic dynamic models for malaria with distributed delays in a non-random environment

A family of deterministic SEIRS epidemic dynamic models for malaria is presented. The family type is determined by a general functional response for the nonlinear incidence rate of the disease. Furthermore, the malaria models exhibit three random delays -- the incubation periods of the plasmodium inside the female mosquito and human hosts, and also the period of effective acquired natural immunity against the disease. Insights about the effects of the delays and the nonlinear incidence rate of the disease on （1） eradication and （2） persistence of malaria in the human population are obtained via analyzing and interpreting the global asymptotic stability results of the disease-free and endemic equilibrium of the system. The basic reproduction numbers and other threshold values for malaria are calculated, and superior threshold conditions for the stability of the equilibria are found. Numerical simulation results are presented.

Analysis of a malaria model with mosquito host choice and bed-net control

A malaria model is formulated which includes the enhanced attractiveness of infectious humans to mosquitoes, as result of host manipulation by malaria parasite, and the human behavior, represented by insecticidetreated bed-nets usage. The occurrence of a backward bifurcation at R0 = 1 is shown to be possible, which implies that multiple endemic equilibria co-exist with a stable disease-free equilibrium when the basic repro- duction number is less than unity. This phenomenon is found to be caused by disease- induced human mortality. The global asymptotic stability of the endemic equilibrium for R0 〉1 is proved, by using the geometric method for global stability. Therefore, the disease becomes endemic for R0〉 1 regardless of the number of initial cases in both the human and vector populations. Finally, the impact on system dynamics of vector＇s host preferences and bed-net usage behavior is investigated.

Epigenetic regulations in immune evasion of the deadliest malaria parasite Plasmodium falciparum

Both eukaryotic and prokaryotic pathogens infect the host stably via an immune evasion mecha- nism termed mutually exclusive expression. Nowadays, little is known about this epigenetic mechanism, largely limiting the understanding of pathogenesis of many bacterial, fungal and protozoan pathogens and therefore the development of novel drugs and vaccines. In the most severe malaria parasite, Plasrnodiurn falciparum, there is a major virulence gene family termed vat, by which the variant antigen PfEMP1 is encoded and expressed on the surface of parasite-infected erythrocytes. Each parasite carries about 60 anti- genically various vat genes, however, only one of which is expressed at a given time during infection. P. falciparum expresses PfEMP1s in this clonally variant manner to bind to different human endothelial re- ceptors, allowing the infected erythrocytes to sequester in tissues to escape the host＇s immune response in- cluding spleen killing and humoral immunity. At present, the mechanism of mutually exclusive expression of the var gene family remains largely unknown, even though there is increasing evidence suggesting im- portant roles of the epigenetic regulation involved in vat gene expression. In addition, epigenetic factors were also found in association with transcriptional regulation of other antigenic variant gene families in P. falciparum. In this paper, we review the current understanding of epigenetic regulations of P. falcipa- rum virulence genes with particular views toward the design of novel vaccines, drugs, and diagnosis to ma- laria.