Objective:To assess the distribution of ABO blood group and their relationship with Plasmodium falciparum(P.falciparum) malaria among febrile outpatients who sought medical attention at Dore Bafeno Health Center,South...Objective:To assess the distribution of ABO blood group and their relationship with Plasmodium falciparum(P.falciparum) malaria among febrile outpatients who sought medical attention at Dore Bafeno Health Center,Southern Ethiopia.Methods:A total of 269 febrile outpatients who visited Dore Bafeno Health Center,Southern Ethiopia,were examined for malaria and also tested for ABO blood groups in January 2010.The blood specimens were collected by finger pricking,stained with Geimsa,and examined microscopically.Positive cases of the parasitemia were counted.CareStart^(TM) Malaria PflPv Combo was also used to test the blood specimens for malaria.ABO blood groups were determined by agglutination test using ERYCLONE antisera.Data on socio-demographic characteristics and treatment status of the participants were also collected.Chi-square and ANOVA tests were used to assess the difference between frequencies and means,respectively.Results:Out of a total of 269 participants,178(66.2%) febrile patients were found to be infected with Plasmodium parasites,among which 146(54.3%),28(10.4%),and 4(1.5%) belonged to P.falciparum,P.vivax,and mixed infections,respectively.All febrile patients were also tested for ABO blood groups and 51.3%,23.5%,21.9%and 3.3%were found to be blood types of 0,A,B and AB,respectively.Both total malaria infection and P.falciparum infection showed significant association with blood types(P<0.05).The proportion of A or B but not 0 phenotypes was higher(P<0.05) in individuals with P.falciparum as compared with non-infected individuals.The chance of having P.falciparum infection in patients with blood groups A,B and AB was 2.5,2.5 and 3.3times more than individuals showing blood 0 phenotypes,respectively.The mean P.falciparum malaria parasitemia for blood groups A,B,AB,and 0 were 3 744/μ L,1 805/ μ L,5 331/μ L,and1 515/μ L,respectively(P<0.01).Conclusions:The present findings indicate that individuals of blood groups A,B and AB are more susceptible to P.falciparum infection as compared with individuals of blood group O.Nevertheless,further in depth studies are required to clearly establish the role that ABO blood group plays in P.falciparum malaria.展开更多
Objective:To illustrate the clinical features and investigate the indicators associated with a fatal outcome in adult patients with severe Plasmodium falciparum malaria admitted to the Hospital for Tropical Diseases,B...Objective:To illustrate the clinical features and investigate the indicators associated with a fatal outcome in adult patients with severe Plasmodium falciparum malaria admitted to the Hospital for Tropical Diseases,Bangkok,Thailand.Methods:We studied 202 adult malaria patients admitted to the Intensive Care Unit.A total of 43 clinical variables were identified by univariate and logistic regression analyses,to eliminate confounding factors.Results:Regarding the statistical methods,only 6 variables-jaundice,cerebral malaria,metabolic acidosis,body mass index,initial respiratory rate,and white blood cell count-were significant indicators of death, with adjusted odds ratios(95%CI) of 15.2(2.1-32.3).4.3(2.3-12.6),3.3(2.3-5.7),2.4(1.9-3.5),2.2 (1.5-2.6),and 1.7(1.2-3.1),respectively.Conclusions:Our study found that jaundice,cerebral malaria,metabolic acidosis,body mass index,initial respiratory rate and white blood cell count were indicators of fatal outcome in severe Plasmodium falciparum malaria.Further studies on the fatal indicators in severe malaria need to be compared with data from different geographical areas,to construct practical measures to address potentially fatal indicators in different settings.展开更多
Objective:Malaria remains the single leading killer of children in sub - Sahara Africa and Schistosomiasis is considered to be second to malaria in global importance.Co - infection of malaria and urinary schistosomias...Objective:Malaria remains the single leading killer of children in sub - Sahara Africa and Schistosomiasis is considered to be second to malaria in global importance.Co - infection of malaria and urinary schistosomiasis has been reported to exacerbate disease morbidity such as anaemia.In different part of the globe,the co - infection between malaria and schistosomiasis provides some protections on the infected persons.The protective effect of this co - infection elucidated immunologically using cytokines is lacking in our locality.Methods:Urine and blood samples obtained from the 160 volunteers were subjected to standard parasitological techniques for diagnosis of urinary schistosomiasis and malaria respectively.Blood samples collected from these volunteers comprising 80 children with schistosomiasis and malaria and the 80 children who had malaria only were subjected to cytokines concentration determination using commercial standard enzyme linked immunosorbent assay kits(Abeam,UK).Results:Eighty participants with co - infection had a mean malarial parasitaemia of 662±201.1μL while the 80 participants with only P.falciparum malaria had a mean malarial parasiteamia of 5943±3270.7μL.Also the volunteers had mean haemoglobin of 11.2 g/dL for co - infected individuals and 5.7 g/dL for participants with single infection of malaria.The serum cytokine levels of the children with S. haematobium and P.falciparum and only P.falciparum infection are as follows;interleukin - 4(16.6 pg/ mL versus 5.2 pg/mL),IL - 5(501.3 pg/mL versus 357.5 pg/mL);IL -8(2 550 pg/mL versus 309 pg/mL),IL - 10(273 pg/mL versus 290 pg/mL),TNF -α(25 pg/mL versus 290 pg/mL) and IFN -γ(21.9 pg/mL versus 2.5 pg/mL).The TNF -α/IL - 10 ratio is 7 for the children with co - infection while those with only P.falciparum malaria infection had a TNF -α/IL - 10 ratio of 0.9.Conclusion:We conclude that the elevated IL - 4,IL - 5,IL - 8 and IFN -γconcentration induced by schistosomiasis altered the Th1/Th 2 profile and protected the children against the morbidity and severity of malaria attack among the children with co - infection.展开更多
Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment.Methods:Adherent human monocytes were fed for 3 hours with different meals(native hemo...Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment.Methods:Adherent human monocytes were fed for 3 hours with different meals(native hemozoin;lipid free hemozoin;and control latex particles),then tumor necrosis factor alpha was monitored in cell supernatants up to 48 hours through western blotting or specific enzyme-linked immunoadsorbent assay.In selected experiments,unfed monocytes were treated with different doses of 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid or 4-hydroxynonenal instead of phagocytosis.Results:Hemozoin-fed monocytes produced higher levels of tumor necrosis factor alpha than unstimulated and latex-fed cells, while lipid-free hemozoin did not reproduce these results.Additionally,hemozoin effects were mimicked dose-dependently by 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid,but not by 4-hydroxynonenal.Conclusions:Present data suggest an essential role for lipids in hemozoindependent enhanced release of tumor necrosis factor alpha from monocytes,and 15(S,R)hydroxy -6,8,11,13-eicosatetraenoic acid could be one possible specific mediator.展开更多
Objective:To determine the prevalence of malaria in Aligarh and analyze species dominance in different years over a decade.Methods:Diagnosis of malaria was done using microscopy as gold standard,rapid antigen detectio...Objective:To determine the prevalence of malaria in Aligarh and analyze species dominance in different years over a decade.Methods:Diagnosis of malaria was done using microscopy as gold standard,rapid antigen detection assays and quantitative buffy coat(QBC) assays.Giemsa stained blood smear examination was done,thick and thin films were examined for presence of different Plasmodium spp.Rapid antigen detection assays employing detection of HRP-2 and parasite lactate dehydrogenase antigen(pLDH) by immunochromatography was done in patients whose blood smear found to be negative by conventional Giemsa slide examination.QBC was done in cases where there is strong clinical suspicion of malaria with blood smear negative,in patients with chronic malaria,splenomegaly,or in those patients who had inadequate treatment and for post-treatment follow up.Results:Plasmodium vivax and Plasmodium falciparum were only species detected in our hospital.Overall prevalence of malaria in Aligarh was found to be 8.8%.The maximum prevalence of 20.1%was observed in year 2008 and lowest 2.3%in 2002. Conclusions:High prevalence of malaria is observed in this part of country with dominance of both species particularly Plasmodium falciparum should be monitored and factors accounting for occurrence should be studied to employ effective control measures.展开更多
Background: Nigeria is currently a malaria endemic country with an estimated 76% of her population at risk of contracting malaria [1]. According to a study in Nigeria, the first line of action mothers took when their ...Background: Nigeria is currently a malaria endemic country with an estimated 76% of her population at risk of contracting malaria [1]. According to a study in Nigeria, the first line of action mothers took when their children under 5 years have malaria showed that over 50% of them used non-prescription drugs they have at home or bought from pharmacy stores. And 60% of the most commonly used drugs for malaria treatment were chloroquine [2]. Many recent studies have demonstrated re-emergence of chloroquine-sensitive P. falciparum, suggesting a possible role in future malaria control [3]. Objective: The aim of this study was to investigate the effect of home-based oral chloroquine treatment among children under 5 years with Plasmodium falciparum malaria attending Jos University Teaching Hospital and OLA Hospital in Jos Metropolis. Method: This is a cross-sectional study of 93 malaria and non-malaria children. Malaria diagnosis was carried out using microscopical examination of Leishman’s stained thick and thin blood films, P. falciparum parasitemia was assessed by standard microscopy techniques and complete blood count was done using Beckman Coulter Analyzer. Results: The body temperature on admission was significantly lower (p ˚C ± 0.07˚C) than in the three malaria groups. The mean body temperature of chloroquine treated children with malaria was significantly lower (p Conclusion: The results obtained in this study demonstrate that there was significant positive impact of chloroquine treatment on Plasmodium falciparum parasitemia and degree of anemia in children under 5 years with Plasmodium falciparum in Jos Metropolis.展开更多
Background:Soil-transmitted helminths(STHs)and Plasmodium falciparum infections remain public health problems in Cameroon.A cross-sectional study was carried out in the Mount Cameroon area to determine the prevalence ...Background:Soil-transmitted helminths(STHs)and Plasmodium falciparum infections remain public health problems in Cameroon.A cross-sectional study was carried out in the Mount Cameroon area to determine the prevalence and intensity of STHs and P.falciparum infections in individuals living in different agroecosystems;to assess the influence of these infections on haematological parameters;and to identify the risk factors associated with STH infections.Methods:STH and malaria parasites were detected using the Kato-Katz method and Giemsa staining of blood films,respectively.Complete blood count values were obtained using an automatic haematology analyser.Soil samples were analysed using the sucrose floatation sedimentation method.Categorical and continuous variables were compared as required and logistic regression models were used to assess the risk factors for STH infections and anaemia.Results:Of the 450 participants examined,STHs,P.falciparum and mixed co-infections were detected in 14.0,33.3 and 5.6%of participants,respectively.Significantly higher prevalences of Ascaris(18.8%)and Trichuris(7.9%)infections were observed in participants from tea plantation areas compared to those from banana and palm plantation areas,with similar trends in egg density.P.falciparum prevalence and parasite density were comparable between the different agroecosystems.The overall prevalence of anaemia was 64.2%.The prevalence of haematological manifestations such as moderate(48.0%)and severe(8.0%)anaemia,leucopenia(26.9%)and microcytosis(30.8%)was significantly higher among Plasmodium-STH co-infected participants.Soil samples from plantations showed the highest prevalences of STH eggs compared to soil samples from areas around pit toilets and public water taps.Living in a tea plantation area(OR=3.07),age(AOR=1.49)and lack of access to potable water(OR=2.25)were identified as risk factors for STH infections,while the age groups 15-25 years(OR=2.928)and 26-35 years(OR=2.832),and being female(OR=2.671)were significant risk factors for anaemia.Conclusions:STHs,malaria and anaemia are still of public health concern in plantation communities.Co-infections negatively influence haematological parameters.The tea farming agroecosystem,age and lack of access to potable water were identified as significant risk factors for STH infections.Trial registration:Not applicable.展开更多
Objective To sequence the gene encoding glutamate rich protein (GLURP) andidentify the genotypes of geographically different Plasmodium falciparum (P. f ) isolatesfrom China. Methods The gene of R2 repeat region...Objective To sequence the gene encoding glutamate rich protein (GLURP) andidentify the genotypes of geographically different Plasmodium falciparum (P. f ) isolatesfrom China. Methods The gene of R2 repeat region of GLURP was amplified by nestedpolymerase chain reaction and cloned into T-vector. The nucleotide sequence of GLURPgene was determined by automatic sequencer (Dideoxy termination method) and analyzed byDNA Star software. Results At least 7 different GLURP genotypes ranging from 600 bpto 1 500 bp were found in Yunnan and Hainan provinces. R2 region of GLURP gene consistedof several repeat units. Each repeat unit was composed of 19-20 residues which were shownto be highly conserved. GLURP gene was also size polymorphic due to differences in thenumber of repeat units, whereas the repeat sequence was conserved. Sequence analysisshowed that DNA sequences and deduced amino acid sequences were highly homologousamong the geographically dispersed isolates or various isolates from the same geographicalregion. No obvious differences were found in the GLURP gene sequences amonggeographically different isolates. Conclusion GLURP gene is highly structure conservedand size polymorphic, and so is useful in searching for malaria vaccine candidate antigen anddeveloping a genotyping method for malaria research.展开更多
Objectives: To explore whether individuals infected with Plasmodium falciparum(P. falciparum) develop antibodies directed against Pf EMP1-DBLa, and to assess their IgG subclass distribution in severe and uncomplicated...Objectives: To explore whether individuals infected with Plasmodium falciparum(P. falciparum) develop antibodies directed against Pf EMP1-DBLa, and to assess their IgG subclass distribution in severe and uncomplicated malaria.Methods: The anti-PfDBLα IgG and their IgG subclass distributions in plasma of severe(SM) and uncomplicated malaria(UCM) were assessed by enzyme-linked immunoabsorbent assay. The antibody profiles to P. falciparum blood stage antigens were evaluated. CD36 binding ability was determined by static receptor-binding assays.Rosette formation was performed by staining with acridine orange.Results: Significantly higher number of UCM(86.48%) than SM(57.78%) plasma contained total acquisition of specific IgG to P. falciparum antigens(P = 0.000). Similar manners were seen in response to P. falciparum DBLa with significant difference(UCM,59.46% vs SM, 40.00%; P = 0.014). Anti-PfDBLα-IgG1 and-IgG3 were the predominant subclasses. Similar percentage of UCM(31.82%) and SM(33.33%) plasma contained only IgG1, while 13.64% of UCM and 27.78% of SM plasma contained only IgG3. AntiPfDBLα-IgG1 coexpressed with more than one subclass was noted(UCM, 27.27%; SM,16.67%). Obviously, IgG1 coexpressed with IgG3(9.09%) was observed in only UCM plasma. IgG1 was coexpressed with IgG2 in UCM(9.09%) and SM(11.11%) plasma,while IgG1 was coexpressed with IgG4 only in UCM plasma(4.55%). IgG subclasses to P. falciparum antigens were distributed in a similar manner. Only the levels of IgG1, but not IgG3 were significantly higher in UCM than in SM.Conclusions: These data suggest that individuals infected with P. falciparum can develop the anti-Pf EMP1 antibodies with the major contribution of specific IgG subclasses. The balance and the levels of anti-PfDBLα IgG subclasses play a crucial role in antibody mediated protection against severe malaria.展开更多
Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum(P. falciparum) malaria although drug resistance has already emerged and spread i...Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum(P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria.展开更多
Malaria is 1 mosquito-borne disease,which is most commonly caused by a parasite called Plasmodium falciparum(P.falciparum).Cerebral malaria is the most severe neurological complication presented in
Objective:Avidly phagocytosed hemozoin(malarial pigment) alters several functions of human monocytes and stimulates generation of several cytokines.Recently,we showed that phagocytosis of hemozoin by human monocytes i...Objective:Avidly phagocytosed hemozoin(malarial pigment) alters several functions of human monocytes and stimulates generation of several cytokines.Recently,we showed that phagocytosis of hemozoin by human monocytes increases expression and activity of matrix metalloproteinase-9,a proteolytic enzyme available in specific gelatinase granules,which contain several enzymes including lysozyme.Present work investigated active lysozyme release after phagocytosis of hemozoin and its dependence on production of tumor necrosis factor alpha. Methods:After phagocytosis of hemozoin,hemozoin-containing trophozoites or control meals(opsonized nonparasitized red blood cells and latex particles),monocyte supematants were monitored for 2 hours,in presence of blocking anti-human tumor necrosis factor alpha antibodies or recombinant human tumor necrosis factor alpha cytokine in selected experiments.Lysozyme release was evaluated by a specific spectrometric assay measuring lysozyme activity after coincubation of cell supematants with suspensions of Mycrococcus Lysodeikticus,while levels of soluble tumor necrosis factor alpha were analyzed by specific enzyme-linked immunodsorbent assay. Results:Levels of lysozyme activity and soluble tumor necrosis factor alpha protein were increased in hemozoin in-or trophozoites-laden monocytes supematants.Phagocytosis per se(control meals) also increased lysozyme release,but levels were significantly lower than those obtained after phagocytosis of hemozoin or trophozoites. Interestingly,all effects on lysozyme release observed after phagocytosis were abrogated by blocking anti-human tumor necrosis factor alpha antibodies,while they were mimicked by recombinant human tumor necrosis factor alpha cytokine.Conclusions:Present work shows that phagocytosis of hemozoin promotes monocyte degranulation and enhances active lysozyme release.The effect requires tumor necrosis factor alpha mediation.展开更多
A synthetic hybrid 45-peptide gene of Plasmodium falciparum (Pf), which encoded two CSP repeated peptides NANP and three merozoite peptides SPf83. 1, SPf55. 1 and SPf35. 1, was cloned in an expression vector pWR450-1,...A synthetic hybrid 45-peptide gene of Plasmodium falciparum (Pf), which encoded two CSP repeated peptides NANP and three merozoite peptides SPf83. 1, SPf55. 1 and SPf35. 1, was cloned in an expression vector pWR450-1, then the recombinant plasmid pWRA was introduced into the attenuated Salmonella typhimurium SL3261. When used as a live vaccine and administered orally (po), intravenously (iv) or intraperitoneally (ip),the recombinant strain was able to live in vivo and elicit specific humoral and cellular immunity in BALB/c mice and rabbits. As oral immunization is safe and effective, it is thought that the live recombinant Salmonella tyPhimurium vaccine may bring the Pf oral live vaccine a step nearer.展开更多
Objective:To investigate the regulation of matrix metalloproteinases(MMPs) and tissue inhibitors of melalloproleinases(TIMPs) in human microvascular endothelium(HMEC-1) exposed to erythrocytes infected by different st...Objective:To investigate the regulation of matrix metalloproteinases(MMPs) and tissue inhibitors of melalloproleinases(TIMPs) in human microvascular endothelium(HMEC-1) exposed to erythrocytes infected by different strains of Plasmodium falciparum(P.falciparum).Methods: HMEC—1 eells were co—incubated for 72 h with erythrocytes infected by late stage trophozoite of D10(chloroquine-sensilive) or W 2(chloroquine-resistant) P.falciparum strains.Cell supernatants were then collected and the levels of pro- or active gelatinases MMP-9 and MMP-2 were evaluated by gelatin zymograpln and densitometry.The release of pro-MMP-9,MMP-3.MMP-1 and TIMP-1 proteins was analyzed by western blotting and densitometry.Results:Infected erythrocytes induced de novo proMMP-9 and MMP-9 release.Neither basal levels of proMMP-2 were altered,nor active MMP-2 was found.MMP-3 and MMP-1 secretion was significant!) enhanced,whereas basal TIMP-1 was unaffected.All effects were similar for both strains. Conclusions:P.falciparum parasites,either chloroquine-sonsitive or -resistant,induce the release of active MMP-9 protein from human microvascular endothelium,by impairing balances between proMMP-9 and its inhibitor,and by enhancing the levels of its activators.This work provides new evidence on MMP involvement in malaria,pointing at MMP-9 as a possible target in adjuvant therapy.展开更多
Electrophoresis-purified human glycophorin A(GPA)was used to produce its derivatives:(1)separation and purification of glycopeptides from GPA were performed after trypsin-digestion:(2)prepanation of GPA antibody and G...Electrophoresis-purified human glycophorin A(GPA)was used to produce its derivatives:(1)separation and purification of glycopeptides from GPA were performed after trypsin-digestion:(2)prepanation of GPA antibody and GPA glycopeptide antibody;(3)preparation of deglycosylatedGPA(dGPA);(4)incorporating GPA or dGPA into human RBC membrane lipids to form twokinds of liposomes.The products described above were used to test Plasmodim falciparumFCC-1/HN merozoites for their ability to invade human erythrocytes.It was found that GPA-liposomes were able to bind with merozoites and dGPA-liposomes had a negative reaction.GPA,GPA glycopeptide,GPA antibody,GPA glycopeptide antibody and GPA-liposome all had the effectto hinder the invasion of merozoites into human erythrocyte,whereas dGPA-liposome had no suchan effect.展开更多
Objective: To characterize the genetic diversity of Plasmodium falciparum ( P. falciparum ) field isolates in children from Lafia, North-central Nigeria, using the highly polymorphic P. falciparum merozoite surface pr...Objective: To characterize the genetic diversity of Plasmodium falciparum ( P. falciparum ) field isolates in children from Lafia, North-central Nigeria, using the highly polymorphic P. falciparum merozoite surface protein 2 (MSP-2) gene as molecular marker. Methods: Three hundred and twenty children were enrolled into the study between 2005 and 2006. These included 140 children who presented with uncomplicated malaria at the Dalhatu Araf Specialist Hospital, Lafia and another 180 children from the study area with asymptomatic infection. DNA was extracted from blood spot on filter paper and MSP-2 genes were genotyped using allele-specific nested PCR in order to analyze the genetic diversity of parasite isolates. Results: A total of 31 and 34 distinct MSP-2 alleles were identified in the asymptomatic and uncomplicated malaria groups respectively. No difference was found between the multiplicity of infection in the asymptomatic group and that of the uncomplicated malaria group ( P >0.05). However, isolates of the FC27 allele type were dominant in the asymptomatic group whereas isolates of the 3D7 allele type were dominant in the uncomplicated malaria group. Conclusions: This study showed a high genetic diversity of P. falciparum isolates in North-central Nigeria and is comparable to reports from similar areas with high malaria transmission intensity.展开更多
Investigation of the intimate relationship between the human malaria parasite Plasmodium falciparum and its Anopheles vector requires the reliable production and isolation of successive sexual stages of the parasite f...Investigation of the intimate relationship between the human malaria parasite Plasmodium falciparum and its Anopheles vector requires the reliable production and isolation of successive sexual stages of the parasite from infected mosquitoes. Such an advance in propagation would benefit a range of molecular, cellular, immunochemical and transmission-blocking research studies. Parasite cultivation, mosquito rearing, infection and subsequent dissection of mosquitoes are all highly technical procedures that require both skill and experience to perform with competence. Furthermore, to produce mosquitoes of an appropriate age to infect during the short period in which parasites are viable for infection demands precise planning in order to coordinate the interacting life cycles of the parasite and vector. Here, a protocol is described for the complete development of P. falciparum within Anopheles stephensi. A very consistent, high level production in vivo of P. falciparum oocysts and sporozoites is demonstrable by dissection of the mosquito midgut and salivary glands, respectively.展开更多
Immune evasion is a strategy used by pathogenic microbes to evade the host immune system in order to ensure successful propagation. Immune evasion is particularly important for the blood stages of Plasmodium falciparu...Immune evasion is a strategy used by pathogenic microbes to evade the host immune system in order to ensure successful propagation. Immune evasion is particularly important for the blood stages of Plasmodium falciparum, the causative agent of the deadly disease malaria tropica. Because Plasmodium blood stage parasites require human erythrocytes for replication, their ability to evade attack by the human immune system is essential for parasite survival. In order to escape immunity-induced killing, the intraerythrocytic parasites have evolved a variety of evasion mechanisms, including expansion of plasmodial surface proteins, organ-specific sequestration of the infected red blood cells and acquisition of immune-regulatory proteins by the parasite. This review aims to highlight recent advances in the molecular understanding of the immune evasion strategies by P. falciparum, including antigenic variation, surface protein polymorphisms and invasion ligand diversification. The review will further discuss new findings on the regulatory mechanisms applied by P. falciparum to avoid lysis by the human complement as well as killing by immune factors of the mosquito vector.展开更多
Background: Drugs that kill or inhibit sexual stages of Plasmodium such as Primaqiune (PQ) could potentially amplify or synergize the impact of first line antimalarials by blocking transmission to mosquitoes. This stu...Background: Drugs that kill or inhibit sexual stages of Plasmodium such as Primaqiune (PQ) could potentially amplify or synergize the impact of first line antimalarials by blocking transmission to mosquitoes. This study examined the effect of Primaquine on gametocyte carriage in the case management of uncomplicated falciparum malaria with artemisinin-based combination therapy (ACT) with the overall purpose of possibly recommending it as an adjunct drug for malaria control. Methods: A total of 181 patients with uncomplicated falciparum malaria, normal glucose-6-phosphate dehydrogenase (G6PD) enzyme levels, and haemoglobin levels ≥ 8 g/dL completed this two-arm randomized blinded clinical trial to test the efficacy of a single dose PQ (0.75 mg/kg) on falciparum gametocytaemia. 88 subjects were assigned to a standard 3-day course of Dihydroartemisinin-Piperaquine (DHP) alone (n = 88) while 93 others had DHP combined with a single dose of PQ on day 3 (n = 93). A 28-day follow-up schedule carried out in the outpatient clinic of a Primary health facility in Vom, Plateau State Nigeria where study participants were seen on days 1, 3, 7 and then weekly to assess the presence of asexual parasites and gametocytes by microscopy. A Kaplan-Meier analysis was employed to determine the survival function of gametocytes on day 3. The data was analyzed using Epi info version 7.1.5. Results: With a gametocyte prevalence of 27.1%, gametocyte carriage rate was lower in the PQ group due to higher probability of clearing gametocytes (Breslow test χ2 = 8.306, df = 1, p = 0.004) and significantly less likely to harbor gametocytes by day 7 when compared to the DHP-alone group (χ2 = 6.218, df = 1, p = 0.013). Conclusion: Addition of single-dose 0.75 mg/kg PQ was associated with reduced gametocyte carriage as a result of faster gametocyte clearance and lower incidence of gametocyte development in DHP-treated patients. PQ as gametocytocidal drug may be useful in combination with artemisinin-based combination therapy (ACT) regimen to clear gametocytes and thereby interrupt malaria transmission to mosquito vector more effectively than ACT alone.展开更多
基金Supported by School of Graduate Studies through Aklilu LemmaInstitute of Pathobiology,Addis Ababa University(No:RDP/Py-014/09)
文摘Objective:To assess the distribution of ABO blood group and their relationship with Plasmodium falciparum(P.falciparum) malaria among febrile outpatients who sought medical attention at Dore Bafeno Health Center,Southern Ethiopia.Methods:A total of 269 febrile outpatients who visited Dore Bafeno Health Center,Southern Ethiopia,were examined for malaria and also tested for ABO blood groups in January 2010.The blood specimens were collected by finger pricking,stained with Geimsa,and examined microscopically.Positive cases of the parasitemia were counted.CareStart^(TM) Malaria PflPv Combo was also used to test the blood specimens for malaria.ABO blood groups were determined by agglutination test using ERYCLONE antisera.Data on socio-demographic characteristics and treatment status of the participants were also collected.Chi-square and ANOVA tests were used to assess the difference between frequencies and means,respectively.Results:Out of a total of 269 participants,178(66.2%) febrile patients were found to be infected with Plasmodium parasites,among which 146(54.3%),28(10.4%),and 4(1.5%) belonged to P.falciparum,P.vivax,and mixed infections,respectively.All febrile patients were also tested for ABO blood groups and 51.3%,23.5%,21.9%and 3.3%were found to be blood types of 0,A,B and AB,respectively.Both total malaria infection and P.falciparum infection showed significant association with blood types(P<0.05).The proportion of A or B but not 0 phenotypes was higher(P<0.05) in individuals with P.falciparum as compared with non-infected individuals.The chance of having P.falciparum infection in patients with blood groups A,B and AB was 2.5,2.5 and 3.3times more than individuals showing blood 0 phenotypes,respectively.The mean P.falciparum malaria parasitemia for blood groups A,B,AB,and 0 were 3 744/μ L,1 805/ μ L,5 331/μ L,and1 515/μ L,respectively(P<0.01).Conclusions:The present findings indicate that individuals of blood groups A,B and AB are more susceptible to P.falciparum infection as compared with individuals of blood group O.Nevertheless,further in depth studies are required to clearly establish the role that ABO blood group plays in P.falciparum malaria.
文摘Objective:To illustrate the clinical features and investigate the indicators associated with a fatal outcome in adult patients with severe Plasmodium falciparum malaria admitted to the Hospital for Tropical Diseases,Bangkok,Thailand.Methods:We studied 202 adult malaria patients admitted to the Intensive Care Unit.A total of 43 clinical variables were identified by univariate and logistic regression analyses,to eliminate confounding factors.Results:Regarding the statistical methods,only 6 variables-jaundice,cerebral malaria,metabolic acidosis,body mass index,initial respiratory rate,and white blood cell count-were significant indicators of death, with adjusted odds ratios(95%CI) of 15.2(2.1-32.3).4.3(2.3-12.6),3.3(2.3-5.7),2.4(1.9-3.5),2.2 (1.5-2.6),and 1.7(1.2-3.1),respectively.Conclusions:Our study found that jaundice,cerebral malaria,metabolic acidosis,body mass index,initial respiratory rate and white blood cell count were indicators of fatal outcome in severe Plasmodium falciparum malaria.Further studies on the fatal indicators in severe malaria need to be compared with data from different geographical areas,to construct practical measures to address potentially fatal indicators in different settings.
文摘Objective:Malaria remains the single leading killer of children in sub - Sahara Africa and Schistosomiasis is considered to be second to malaria in global importance.Co - infection of malaria and urinary schistosomiasis has been reported to exacerbate disease morbidity such as anaemia.In different part of the globe,the co - infection between malaria and schistosomiasis provides some protections on the infected persons.The protective effect of this co - infection elucidated immunologically using cytokines is lacking in our locality.Methods:Urine and blood samples obtained from the 160 volunteers were subjected to standard parasitological techniques for diagnosis of urinary schistosomiasis and malaria respectively.Blood samples collected from these volunteers comprising 80 children with schistosomiasis and malaria and the 80 children who had malaria only were subjected to cytokines concentration determination using commercial standard enzyme linked immunosorbent assay kits(Abeam,UK).Results:Eighty participants with co - infection had a mean malarial parasitaemia of 662±201.1μL while the 80 participants with only P.falciparum malaria had a mean malarial parasiteamia of 5943±3270.7μL.Also the volunteers had mean haemoglobin of 11.2 g/dL for co - infected individuals and 5.7 g/dL for participants with single infection of malaria.The serum cytokine levels of the children with S. haematobium and P.falciparum and only P.falciparum infection are as follows;interleukin - 4(16.6 pg/ mL versus 5.2 pg/mL),IL - 5(501.3 pg/mL versus 357.5 pg/mL);IL -8(2 550 pg/mL versus 309 pg/mL),IL - 10(273 pg/mL versus 290 pg/mL),TNF -α(25 pg/mL versus 290 pg/mL) and IFN -γ(21.9 pg/mL versus 2.5 pg/mL).The TNF -α/IL - 10 ratio is 7 for the children with co - infection while those with only P.falciparum malaria infection had a TNF -α/IL - 10 ratio of 0.9.Conclusion:We conclude that the elevated IL - 4,IL - 5,IL - 8 and IFN -γconcentration induced by schistosomiasis altered the Th1/Th 2 profile and protected the children against the morbidity and severity of malaria attack among the children with co - infection.
基金supported in the context of the Italian Malaria Network by grants from Compagnia di San Paolo-IMI and from Regione Piemonte,Ricerca Sanitaria Finalizzata 2008bis to PA
文摘Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment.Methods:Adherent human monocytes were fed for 3 hours with different meals(native hemozoin;lipid free hemozoin;and control latex particles),then tumor necrosis factor alpha was monitored in cell supernatants up to 48 hours through western blotting or specific enzyme-linked immunoadsorbent assay.In selected experiments,unfed monocytes were treated with different doses of 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid or 4-hydroxynonenal instead of phagocytosis.Results:Hemozoin-fed monocytes produced higher levels of tumor necrosis factor alpha than unstimulated and latex-fed cells, while lipid-free hemozoin did not reproduce these results.Additionally,hemozoin effects were mimicked dose-dependently by 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid,but not by 4-hydroxynonenal.Conclusions:Present data suggest an essential role for lipids in hemozoindependent enhanced release of tumor necrosis factor alpha from monocytes,and 15(S,R)hydroxy -6,8,11,13-eicosatetraenoic acid could be one possible specific mediator.
基金financial help from SERC Fast Track Scheme,Department of science and Technology (DST),New Delhi,India
文摘Objective:To determine the prevalence of malaria in Aligarh and analyze species dominance in different years over a decade.Methods:Diagnosis of malaria was done using microscopy as gold standard,rapid antigen detection assays and quantitative buffy coat(QBC) assays.Giemsa stained blood smear examination was done,thick and thin films were examined for presence of different Plasmodium spp.Rapid antigen detection assays employing detection of HRP-2 and parasite lactate dehydrogenase antigen(pLDH) by immunochromatography was done in patients whose blood smear found to be negative by conventional Giemsa slide examination.QBC was done in cases where there is strong clinical suspicion of malaria with blood smear negative,in patients with chronic malaria,splenomegaly,or in those patients who had inadequate treatment and for post-treatment follow up.Results:Plasmodium vivax and Plasmodium falciparum were only species detected in our hospital.Overall prevalence of malaria in Aligarh was found to be 8.8%.The maximum prevalence of 20.1%was observed in year 2008 and lowest 2.3%in 2002. Conclusions:High prevalence of malaria is observed in this part of country with dominance of both species particularly Plasmodium falciparum should be monitored and factors accounting for occurrence should be studied to employ effective control measures.
文摘Background: Nigeria is currently a malaria endemic country with an estimated 76% of her population at risk of contracting malaria [1]. According to a study in Nigeria, the first line of action mothers took when their children under 5 years have malaria showed that over 50% of them used non-prescription drugs they have at home or bought from pharmacy stores. And 60% of the most commonly used drugs for malaria treatment were chloroquine [2]. Many recent studies have demonstrated re-emergence of chloroquine-sensitive P. falciparum, suggesting a possible role in future malaria control [3]. Objective: The aim of this study was to investigate the effect of home-based oral chloroquine treatment among children under 5 years with Plasmodium falciparum malaria attending Jos University Teaching Hospital and OLA Hospital in Jos Metropolis. Method: This is a cross-sectional study of 93 malaria and non-malaria children. Malaria diagnosis was carried out using microscopical examination of Leishman’s stained thick and thin blood films, P. falciparum parasitemia was assessed by standard microscopy techniques and complete blood count was done using Beckman Coulter Analyzer. Results: The body temperature on admission was significantly lower (p ˚C ± 0.07˚C) than in the three malaria groups. The mean body temperature of chloroquine treated children with malaria was significantly lower (p Conclusion: The results obtained in this study demonstrate that there was significant positive impact of chloroquine treatment on Plasmodium falciparum parasitemia and degree of anemia in children under 5 years with Plasmodium falciparum in Jos Metropolis.
基金This work was supported by the special fund for research and modernisation given to the authors by the Government of Cameroon。
文摘Background:Soil-transmitted helminths(STHs)and Plasmodium falciparum infections remain public health problems in Cameroon.A cross-sectional study was carried out in the Mount Cameroon area to determine the prevalence and intensity of STHs and P.falciparum infections in individuals living in different agroecosystems;to assess the influence of these infections on haematological parameters;and to identify the risk factors associated with STH infections.Methods:STH and malaria parasites were detected using the Kato-Katz method and Giemsa staining of blood films,respectively.Complete blood count values were obtained using an automatic haematology analyser.Soil samples were analysed using the sucrose floatation sedimentation method.Categorical and continuous variables were compared as required and logistic regression models were used to assess the risk factors for STH infections and anaemia.Results:Of the 450 participants examined,STHs,P.falciparum and mixed co-infections were detected in 14.0,33.3 and 5.6%of participants,respectively.Significantly higher prevalences of Ascaris(18.8%)and Trichuris(7.9%)infections were observed in participants from tea plantation areas compared to those from banana and palm plantation areas,with similar trends in egg density.P.falciparum prevalence and parasite density were comparable between the different agroecosystems.The overall prevalence of anaemia was 64.2%.The prevalence of haematological manifestations such as moderate(48.0%)and severe(8.0%)anaemia,leucopenia(26.9%)and microcytosis(30.8%)was significantly higher among Plasmodium-STH co-infected participants.Soil samples from plantations showed the highest prevalences of STH eggs compared to soil samples from areas around pit toilets and public water taps.Living in a tea plantation area(OR=3.07),age(AOR=1.49)and lack of access to potable water(OR=2.25)were identified as risk factors for STH infections,while the age groups 15-25 years(OR=2.928)and 26-35 years(OR=2.832),and being female(OR=2.671)were significant risk factors for anaemia.Conclusions:STHs,malaria and anaemia are still of public health concern in plantation communities.Co-infections negatively influence haematological parameters.The tea farming agroecosystem,age and lack of access to potable water were identified as significant risk factors for STH infections.Trial registration:Not applicable.
文摘Objective To sequence the gene encoding glutamate rich protein (GLURP) andidentify the genotypes of geographically different Plasmodium falciparum (P. f ) isolatesfrom China. Methods The gene of R2 repeat region of GLURP was amplified by nestedpolymerase chain reaction and cloned into T-vector. The nucleotide sequence of GLURPgene was determined by automatic sequencer (Dideoxy termination method) and analyzed byDNA Star software. Results At least 7 different GLURP genotypes ranging from 600 bpto 1 500 bp were found in Yunnan and Hainan provinces. R2 region of GLURP gene consistedof several repeat units. Each repeat unit was composed of 19-20 residues which were shownto be highly conserved. GLURP gene was also size polymorphic due to differences in thenumber of repeat units, whereas the repeat sequence was conserved. Sequence analysisshowed that DNA sequences and deduced amino acid sequences were highly homologousamong the geographically dispersed isolates or various isolates from the same geographicalregion. No obvious differences were found in the GLURP gene sequences amonggeographically different isolates. Conclusion GLURP gene is highly structure conservedand size polymorphic, and so is useful in searching for malaria vaccine candidate antigen anddeveloping a genotyping method for malaria research.
基金supported by Thailand Research Fund(Project number:MRG5480003)
文摘Objectives: To explore whether individuals infected with Plasmodium falciparum(P. falciparum) develop antibodies directed against Pf EMP1-DBLa, and to assess their IgG subclass distribution in severe and uncomplicated malaria.Methods: The anti-PfDBLα IgG and their IgG subclass distributions in plasma of severe(SM) and uncomplicated malaria(UCM) were assessed by enzyme-linked immunoabsorbent assay. The antibody profiles to P. falciparum blood stage antigens were evaluated. CD36 binding ability was determined by static receptor-binding assays.Rosette formation was performed by staining with acridine orange.Results: Significantly higher number of UCM(86.48%) than SM(57.78%) plasma contained total acquisition of specific IgG to P. falciparum antigens(P = 0.000). Similar manners were seen in response to P. falciparum DBLa with significant difference(UCM,59.46% vs SM, 40.00%; P = 0.014). Anti-PfDBLα-IgG1 and-IgG3 were the predominant subclasses. Similar percentage of UCM(31.82%) and SM(33.33%) plasma contained only IgG1, while 13.64% of UCM and 27.78% of SM plasma contained only IgG3. AntiPfDBLα-IgG1 coexpressed with more than one subclass was noted(UCM, 27.27%; SM,16.67%). Obviously, IgG1 coexpressed with IgG3(9.09%) was observed in only UCM plasma. IgG1 was coexpressed with IgG2 in UCM(9.09%) and SM(11.11%) plasma,while IgG1 was coexpressed with IgG4 only in UCM plasma(4.55%). IgG subclasses to P. falciparum antigens were distributed in a similar manner. Only the levels of IgG1, but not IgG3 were significantly higher in UCM than in SM.Conclusions: These data suggest that individuals infected with P. falciparum can develop the anti-Pf EMP1 antibodies with the major contribution of specific IgG subclasses. The balance and the levels of anti-PfDBLα IgG subclasses play a crucial role in antibody mediated protection against severe malaria.
基金supported by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (CHEMAL, TDR/WHO)the National Science and Technology Development Agency of Thailand (NSTDA Career Development Award)+2 种基金the Thailand Research Fund (TRF Basic Research)the Office of Higher Education Commission (OHEC University Staff Development Consortium)Graduate School and Faculty of Medicine, Chulalongkorn University, Thailand
文摘Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum(P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria.
文摘Malaria is 1 mosquito-borne disease,which is most commonly caused by a parasite called Plasmodium falciparum(P.falciparum).Cerebral malaria is the most severe neurological complication presented in
基金supported in the context of the Italian Malaria Network by grants from Compagnia di San Paolo-IMIthe University of Torino Intramural FundsRegione Piemonte,Ricerca Sanitaria Finalizzata 2007 to PA
文摘Objective:Avidly phagocytosed hemozoin(malarial pigment) alters several functions of human monocytes and stimulates generation of several cytokines.Recently,we showed that phagocytosis of hemozoin by human monocytes increases expression and activity of matrix metalloproteinase-9,a proteolytic enzyme available in specific gelatinase granules,which contain several enzymes including lysozyme.Present work investigated active lysozyme release after phagocytosis of hemozoin and its dependence on production of tumor necrosis factor alpha. Methods:After phagocytosis of hemozoin,hemozoin-containing trophozoites or control meals(opsonized nonparasitized red blood cells and latex particles),monocyte supematants were monitored for 2 hours,in presence of blocking anti-human tumor necrosis factor alpha antibodies or recombinant human tumor necrosis factor alpha cytokine in selected experiments.Lysozyme release was evaluated by a specific spectrometric assay measuring lysozyme activity after coincubation of cell supematants with suspensions of Mycrococcus Lysodeikticus,while levels of soluble tumor necrosis factor alpha were analyzed by specific enzyme-linked immunodsorbent assay. Results:Levels of lysozyme activity and soluble tumor necrosis factor alpha protein were increased in hemozoin in-or trophozoites-laden monocytes supematants.Phagocytosis per se(control meals) also increased lysozyme release,but levels were significantly lower than those obtained after phagocytosis of hemozoin or trophozoites. Interestingly,all effects on lysozyme release observed after phagocytosis were abrogated by blocking anti-human tumor necrosis factor alpha antibodies,while they were mimicked by recombinant human tumor necrosis factor alpha cytokine.Conclusions:Present work shows that phagocytosis of hemozoin promotes monocyte degranulation and enhances active lysozyme release.The effect requires tumor necrosis factor alpha mediation.
文摘A synthetic hybrid 45-peptide gene of Plasmodium falciparum (Pf), which encoded two CSP repeated peptides NANP and three merozoite peptides SPf83. 1, SPf55. 1 and SPf35. 1, was cloned in an expression vector pWR450-1, then the recombinant plasmid pWRA was introduced into the attenuated Salmonella typhimurium SL3261. When used as a live vaccine and administered orally (po), intravenously (iv) or intraperitoneally (ip),the recombinant strain was able to live in vivo and elicit specific humoral and cellular immunity in BALB/c mice and rabbits. As oral immunization is safe and effective, it is thought that the live recombinant Salmonella tyPhimurium vaccine may bring the Pf oral live vaccine a step nearer.
基金supported by Universita di Milano(PUR.2009) to Nicoletta Basilico and Charity Funds from Mrs.Franca Squazza to Mauro PratoMauro Prato holds a professorshipgranted by Universita Torino and Azienda Sanitaria Locale-19(ASL-19)
文摘Objective:To investigate the regulation of matrix metalloproteinases(MMPs) and tissue inhibitors of melalloproleinases(TIMPs) in human microvascular endothelium(HMEC-1) exposed to erythrocytes infected by different strains of Plasmodium falciparum(P.falciparum).Methods: HMEC—1 eells were co—incubated for 72 h with erythrocytes infected by late stage trophozoite of D10(chloroquine-sensilive) or W 2(chloroquine-resistant) P.falciparum strains.Cell supernatants were then collected and the levels of pro- or active gelatinases MMP-9 and MMP-2 were evaluated by gelatin zymograpln and densitometry.The release of pro-MMP-9,MMP-3.MMP-1 and TIMP-1 proteins was analyzed by western blotting and densitometry.Results:Infected erythrocytes induced de novo proMMP-9 and MMP-9 release.Neither basal levels of proMMP-2 were altered,nor active MMP-2 was found.MMP-3 and MMP-1 secretion was significant!) enhanced,whereas basal TIMP-1 was unaffected.All effects were similar for both strains. Conclusions:P.falciparum parasites,either chloroquine-sonsitive or -resistant,induce the release of active MMP-9 protein from human microvascular endothelium,by impairing balances between proMMP-9 and its inhibitor,and by enhancing the levels of its activators.This work provides new evidence on MMP involvement in malaria,pointing at MMP-9 as a possible target in adjuvant therapy.
文摘Electrophoresis-purified human glycophorin A(GPA)was used to produce its derivatives:(1)separation and purification of glycopeptides from GPA were performed after trypsin-digestion:(2)prepanation of GPA antibody and GPA glycopeptide antibody;(3)preparation of deglycosylatedGPA(dGPA);(4)incorporating GPA or dGPA into human RBC membrane lipids to form twokinds of liposomes.The products described above were used to test Plasmodim falciparumFCC-1/HN merozoites for their ability to invade human erythrocytes.It was found that GPA-liposomes were able to bind with merozoites and dGPA-liposomes had a negative reaction.GPA,GPA glycopeptide,GPA antibody,GPA glycopeptide antibody and GPA-liposome all had the effectto hinder the invasion of merozoites into human erythrocyte,whereas dGPA-liposome had no suchan effect.
基金supported by a Deutscher Akademischer Austausch Dienst (DAAD) Research Fellowship as well as a Staff Training Grant from Bells University of Technology, Ota, Nigeria
文摘Objective: To characterize the genetic diversity of Plasmodium falciparum ( P. falciparum ) field isolates in children from Lafia, North-central Nigeria, using the highly polymorphic P. falciparum merozoite surface protein 2 (MSP-2) gene as molecular marker. Methods: Three hundred and twenty children were enrolled into the study between 2005 and 2006. These included 140 children who presented with uncomplicated malaria at the Dalhatu Araf Specialist Hospital, Lafia and another 180 children from the study area with asymptomatic infection. DNA was extracted from blood spot on filter paper and MSP-2 genes were genotyped using allele-specific nested PCR in order to analyze the genetic diversity of parasite isolates. Results: A total of 31 and 34 distinct MSP-2 alleles were identified in the asymptomatic and uncomplicated malaria groups respectively. No difference was found between the multiplicity of infection in the asymptomatic group and that of the uncomplicated malaria group ( P >0.05). However, isolates of the FC27 allele type were dominant in the asymptomatic group whereas isolates of the 3D7 allele type were dominant in the uncomplicated malaria group. Conclusions: This study showed a high genetic diversity of P. falciparum isolates in North-central Nigeria and is comparable to reports from similar areas with high malaria transmission intensity.
文摘Investigation of the intimate relationship between the human malaria parasite Plasmodium falciparum and its Anopheles vector requires the reliable production and isolation of successive sexual stages of the parasite from infected mosquitoes. Such an advance in propagation would benefit a range of molecular, cellular, immunochemical and transmission-blocking research studies. Parasite cultivation, mosquito rearing, infection and subsequent dissection of mosquitoes are all highly technical procedures that require both skill and experience to perform with competence. Furthermore, to produce mosquitoes of an appropriate age to infect during the short period in which parasites are viable for infection demands precise planning in order to coordinate the interacting life cycles of the parasite and vector. Here, a protocol is described for the complete development of P. falciparum within Anopheles stephensi. A very consistent, high level production in vivo of P. falciparum oocysts and sporozoites is demonstrable by dissection of the mosquito midgut and salivary glands, respectively.
文摘Immune evasion is a strategy used by pathogenic microbes to evade the host immune system in order to ensure successful propagation. Immune evasion is particularly important for the blood stages of Plasmodium falciparum, the causative agent of the deadly disease malaria tropica. Because Plasmodium blood stage parasites require human erythrocytes for replication, their ability to evade attack by the human immune system is essential for parasite survival. In order to escape immunity-induced killing, the intraerythrocytic parasites have evolved a variety of evasion mechanisms, including expansion of plasmodial surface proteins, organ-specific sequestration of the infected red blood cells and acquisition of immune-regulatory proteins by the parasite. This review aims to highlight recent advances in the molecular understanding of the immune evasion strategies by P. falciparum, including antigenic variation, surface protein polymorphisms and invasion ligand diversification. The review will further discuss new findings on the regulatory mechanisms applied by P. falciparum to avoid lysis by the human complement as well as killing by immune factors of the mosquito vector.
文摘Background: Drugs that kill or inhibit sexual stages of Plasmodium such as Primaqiune (PQ) could potentially amplify or synergize the impact of first line antimalarials by blocking transmission to mosquitoes. This study examined the effect of Primaquine on gametocyte carriage in the case management of uncomplicated falciparum malaria with artemisinin-based combination therapy (ACT) with the overall purpose of possibly recommending it as an adjunct drug for malaria control. Methods: A total of 181 patients with uncomplicated falciparum malaria, normal glucose-6-phosphate dehydrogenase (G6PD) enzyme levels, and haemoglobin levels ≥ 8 g/dL completed this two-arm randomized blinded clinical trial to test the efficacy of a single dose PQ (0.75 mg/kg) on falciparum gametocytaemia. 88 subjects were assigned to a standard 3-day course of Dihydroartemisinin-Piperaquine (DHP) alone (n = 88) while 93 others had DHP combined with a single dose of PQ on day 3 (n = 93). A 28-day follow-up schedule carried out in the outpatient clinic of a Primary health facility in Vom, Plateau State Nigeria where study participants were seen on days 1, 3, 7 and then weekly to assess the presence of asexual parasites and gametocytes by microscopy. A Kaplan-Meier analysis was employed to determine the survival function of gametocytes on day 3. The data was analyzed using Epi info version 7.1.5. Results: With a gametocyte prevalence of 27.1%, gametocyte carriage rate was lower in the PQ group due to higher probability of clearing gametocytes (Breslow test χ2 = 8.306, df = 1, p = 0.004) and significantly less likely to harbor gametocytes by day 7 when compared to the DHP-alone group (χ2 = 6.218, df = 1, p = 0.013). Conclusion: Addition of single-dose 0.75 mg/kg PQ was associated with reduced gametocyte carriage as a result of faster gametocyte clearance and lower incidence of gametocyte development in DHP-treated patients. PQ as gametocytocidal drug may be useful in combination with artemisinin-based combination therapy (ACT) regimen to clear gametocytes and thereby interrupt malaria transmission to mosquito vector more effectively than ACT alone.
