Malarial pigment does not induce MMP-2 and TIMP-2 protein release by human monocytes

Dear editor, In the recent years growing evidence on the involvement of human matrix metalloproteinases(MMPs) and tissue inhibitors of metalloproteinases(TIMPs) in cerebral malaria (CM) has been reported[1]and a role for malarial pigment haemozoin(HZ) has been proposed[2,3].In a recent work my group showed that in human microvascular endothelial

Recent advances on vaccines against malaria: A review

This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines.Data on malaria vaccine development was collected through a comprehensive review.The literature search was performed using databases including Google Scholar,PubMed,NIH,and Web of Science.Various novel approaches of vaccination are being developed,including those based on radiation-attenuated strategies,monoclonal antibodies,targeted immunogenic peptides,RNA and DNA vaccines,nanoparticle-based vaccines,protein-based vaccination protocols,and whole organism-based vaccination strategies.Trials on RTS,S have entered phase Ⅲtesting,and those based on blood-stage vaccines and vaccines to interrupt malarial transmission have advanced to higher stages of trials.Mathematical modeling,combined drug and vaccine strategies,mass drug administration,polyvalent vaccine formulations,and targeted vaccination campaigns is playing an important role in malarial prevention.Furthermore,assessing coverage,accessibility,acceptability,deployment,compilation,and adherence to specific vaccination strategies in endemic regions is essential for vaccination drives against malaria.

Cold Agglutinin Disease Prevalence and Immunoglobulin M levels in Patients with Splenomegaly from Endemic Areas for Malaria in Rwanda

Background: Inhabitants from malaria endemic zones often present with enlarged spleen, mainly due to hyper reactive malarial splenomegaly (HMS), and it is seen more commonly associated with elevated levels of Immunoglobulin M (IgM). Cold agglutinin disease is an acquired autoimmune hemolytic anemia (AIHA) that is usually due to cold-reacting IgM autoantibodies directed against red cell antigens. The study was conducted in response to the observed high frequency of transfusion dependent anemia in patients with splenomegaly from malaria endemic zones in southern province of Rwanda. The objectives of this study were to determine the prevalence of cold agglutinin disease and to assess the distribution of IgM antibodies among these patients. Methodology: This was a descriptive, cross-sectional study conducted over a period of six months from June 2016 to December 2016. The study enrolled adult population from malaria endemic areas of the southern province of Rwanda with unexplained splenomegaly. Blood samples for testing IgM levels, cold agglutinin, FBC, and markers of hemolysis were collected from peripheral health settings and analyzed at the laboratory of Butare University Teaching Hospital. Results: During the study period, we enrolled 188 participants with enlarged spleen. One hundred twenty-five (66%) were females and 34% were males. The mean (±SD) age of the study participants was 35.6 ± 15.2 years. Out of 188 participants, only 4.8% were found with significantly positive Cold Agglutinin Titer (CAT) (≥1:64) and 84% of participants were found to have elevated serum IgM level. Hemoglobin level, white blood count and platelets count decrease with severity of splenomegaly, while IgM level increases with spleen size. Conclusion: Among patients with splenomegaly from malaria endemic areas, IgM levels correlate with the stages of splenomegaly while cold agglutinin disease plays a small role in the etiology of anemia.

Mosquito larvicidal and pupicidal activity of Euphorbia hirta Linn.(Family:Euphorbiaceae) and Bacillus sphaericus against Anopheles stephensi Liston.(Diptera:Culicidae)

Objective:To explore the larvicidal and pupicidal activity of Euphorbia hirta（E.hirta） leaf extract and Bacillus sphaericus（B.sphaericus） against the malarial vector.Anopheles siephensi（An. stephensi）.Methods:The larvicidal and pupicidal activity was assayed against An.stephensi at various concentrations ranging from（75-375 ppm） under the laboratory as well as field conditions. The LC50 and LC90 value of the E.hirta leaf extract was determined by probit analysis.Results: The plant extract showed larvicidal effects after 24 h of exposure;however,the highest larval mortality was found in the methanol extract of E.hirta against the first to fourth instars larvae and pupae of values LC50=137.40,172.65,217.81,269.37 and 332.39 ppm;B.sphaericus against the first to fourth instars larvae and pupae of values LC50= 44.29,55.83,68.51,82.19 and 95.55 ppm, respectively.Moreover,combined treatment of values of LC50= 79.13,80.42,86.01,93.00 and 98.12 ppm,respectively.No mortality was observed in the control.Conclusions:These results suggest methanol leaf extracts of E.hirta and B.sphaericus have potential to be used as an ideal ecofriendly approach for the control of the malarial vector.An.stephensi as target species of vector control programs.This study provides the first report on the combined mosquito larvicidal and pupicidal activity of this plant crude extract and bacterial toxin against An.stephensi mosquitoes.

The development of a recombinant hybrid protein of Plasmodium falciparum and analysis of its antigenicity and protectivity

A hybrid gene encoding several putative protective epitopes from erythrocytic stage antigens (MSA1,MSA2 and RESA) of P. falciparum as well as exgenous T cell enhancer epitopes from interleukin-1 and tetanus toxin was synthesized chemically. This gene (named HGFC) was cloned and connected with another hybrid gene (HPFA) synthesized previously to make a bigger hybrid gene (HGFCAC). HGFC and HGFCAC were cloned in an expression vector pWR450-1 and transformed into E. Coli JM109. The engineered bacteria could express fusion proteins with molecular weights of 65 and 77 kDa after inducing with isopropylthio-β-D-galactoside (IPTG). The expression rate was about 35% of total bacterial proteins. The expressed products showed sepcific immunological reaction with rabbit antibodies against P. falciparum peptide Glu-Glu-Asn-Val-Glu-His-Asp-Ala (EENVEHDA)by Western blotting. The fusion proteins were pruified by precipitation with amonium sulfate. gel filtration and ion-exchange chromatography and the purity was 82%. The purified protein reacted specifically with mouse immune serum against falciparum blood stage antigens by dot enzyme-linked immunosorbent assay (dot-ELISA).The fusion protein was emulsified with Freund's complete adjuvant (FCA) and used to immunize rabbits. The immune serum can recognize P. falciparum erythrocytic stage antigens of Fcc-1/HN strain and Yunnan strain and had weak cross reaction with P. vivax,but had no reaction with P. cynomlogi and P. berghei antigens. The protective effect of the antibody was tested by in vitro inhibition test to cultured falciparum parasites. Preliminary results indicated that the immune sera could effectively reduce the invasion rates of the parasites to red blood cells and inhibit the growth of the in vitro cultured falciparum parasites. The inhibitory capacity of the immune sera to parasite invasion is enhanced as the amount of the sera increases and the incubation time of the sera with the parasites is prolonged.It was shown that after 72 h incubation at 20% concentration with the parasites, the serum can suppress the multiplication of P.falciparum growth in vitro to a level of 80%.The immune sera caused dispersion of the parasite cytoplasm,atrophy of parasites,agglutination of free merozoites and degeneration of schizonts.

Subcloning and expression of two conserved regions （Ⅰ，Ⅴ） onP190 antigen of Plasmodium falciparum in E．coli

Two DNA fragments, designated as P190CRI (AA1-55) and P190CRV (AA1597-1667)respectively, which encode amino acid residues of conserved region Ⅰ and Ⅴ on the P190 antigen were amplified by polymerase chain reaction from genomic DNA in FCCl/HN strain of Plasmodium falciparum isolated from Hainan Province, China. It was found that there were five base substitutions in the P190CR V, in comparison with the nucleotide sequences of MAD20 strain. These two fragments sequenced were inserted into pGEX-2T plasmid. E. coli JM109 (DE3) were transformed with the recombinant plasmids and the parental plasmid. The results showed that the two fragments were expressed as high-level C-terminal fusions with glutathione S-transferase (GST). The fusion proteins were easily purified from bacterial lysates by affinity chromatography using glutathione Sepharose 4B.

Impact of community-based interventions for the prevention and control of malaria on intervention coverage and health outcomes for the prevention and control of malaria

In this paper,we aim to evaluate the effectiveness of community-based interventions(CBIs)for the prevention and management of malaria.We conducted a systematic review and identified 42 studies for inclusion.Twenty-five of the included studies evaluated the impact of the community-based distribution of insecticide-treated nets(ITNs),indoor residual spraying(IRS),or impregnated bed sheets;14 studies evaluated intermittent preventive therapy(IPT)delivered in community settings;two studies focused on community-based education for malaria prevention;and one study evaluated environmental management through drain cleaning.Our analysis suggests that,overall,the community-based delivery of interventions to prevent and control malaria resulted in a significant increase in ITNs ownership(RR:2.16,95%CI:1.86,2.52)and usage(RR:1.77,95%CI:1.48,2.11).However,usage of ITNs was limited to two-thirds of the population who owned them.Community-based strategies also led to a significant decrease in parasitemia(RR:0.56,95%CI:0.42,0.74),malaria prevalence(RR:0.46,95%CI:0.29,0.73),malaria incidence(RR:0.70,95%CI:0.54,0.90),and anemia prevalence(RR:0.79,95%CI:0.64,0.97).We found a non-significant impact on splenomegaly,birth outcomes(low birth weight,prematurity,stillbirth/miscarriage),anthropometric measures(stunting,wasting,and underweight),and mortality(all-cause and malaria-specific).The subgroup analysis suggested that community-based distribution of ITNs,impregnated bed sheets and IRS,and IPT are effective strategies.Qualitative synthesis suggests that high coverage could be achieved at a lower cost with the integration of CBIs with existing antenatal care and immunization campaigns.Community-based delivery of interventions to prevent and control malaria are effective strategies to improve coverage and access and reduce malaria burden,however,efforts should also be concerted to prevent over diagnosis and drug resistance.

The Analysis of Results of Surveillance on Malaria for the Chinese Workers Who Worked in Gabon

The retrospect investigation for 127 returned Chinese labor services who worked in Gabon were carried out, and malaria blood smear, blood serum test were carried out. There were 32 workers got malaria, the proportion was 25. 2 per cent. For three of the patients, the malarial parasite test presented positive reaction, and the superintendence of quarantine doctor, they were isolated to cure. During the three patients had another suffering from malaria fever,they took antimalaria medicine, their symptom was improved, the course of disease was reduced, and the curative affect was obvious. For the Chinese labor services who go to the serious malaria country, it is important that the health protection of travel medicine should be done well.