Prevalence of Malaria in Pregnant Women in Lagos, South-West Nigeria

Prevalence rates reported for malaria in pregnancy in Nigeria vary considerably. The accuracy of results of malaria diagnosis is dependent on training, experience, and motivation of the microscopist as well as the laboratory facility available. Results of training programmes on malaria microscopy have shown low levels of sensitivity and specificity of those involved in malaria diagnosis routinely and for research. This study was done to ascertain the true prevalence of malaria in pregnancy in Lagos, South-West Nigeria. A total of 1,084 pregnant women were recruited into this study. Blood smears stained with Giemsa were used for malaria diagnosis by light microscopy. Malaria infection during pregnancy presents mostly as asymptomatic infection. The prevalence of malaria in this population was 7.7% (95% confidence interval; 6.2-9.4%). Factors identified to increase the risk of malaria infection include young maternal age (< 20 years), and gravidity (primigravida). In conclusion, this study exposes the over-diagnosis of malaria in pregnancy and the need for training and retraining of laboratory staffs as well as establishing the malaria diagnosis quality assurance programme to ensure the accuracy of malaria microscopy results at all levels.     

The Anopheles gambiae cE5 salivary protein: a sensitive biomarker to evaluate the efficacy of insecticide-treated nets in malaria vector control

Evaluation of vector control is crucial for improving malaria containment and, according to World Health Organization, new complementary indicators would be very valuable. In this study the IgG response to the Anopheles-specific cE5 salivary protein was tested as a tool to evaluate the efficacy of insecticide-treated nets in reducing human exposure to malaria vectors. Sera collected during a longitudinal study carried out in Angola, and including entomological and parasitological data, were used to assess the IgG response to the Anopheles gambiae cE5 in both children and adults, before and after the application of insecticide-treated nets. Seasonal fluctuation of specific IgG antibody levels according to exposure was only found in children (up to ≈14 years old) whose anti-cE5 IgG response dropped after bed nets installation. These results were fully consistent with previous findings obtained with the same set of sera and indicating a substantial reduction of human-vector contact shortly after nets implementation. Overall, children IgG response to the cE5 protein appeared a very sensitive biomarker, which allowed for the detection of even weak exposure to Anopheles bites, indicating it may represent a reliable additional tool to evaluate the efficacy of vector control interventions.     

The effects of mosquito transmission and population bottlenecking on virulence, multiplication rate and rosetting in rodent malaria

Malaria parasites vary in virulence, but the effects of mosquito transmission on virulence phenotypes have not been systematically analysed. Using six lines of malaria parasite that varied widely in virulence, three of which had been serially blood-stage passaged many times, we found that mosquito transmission led to a general reduction in malaria virulence. Despite that, the between-line variation in virulence remained. Forcing serially passaged lines through extreme population bottlenecks (<5 parasites) reduced virulence in only one of two lines. That reduction was to a level intermediate between that of the virulent parental and avirulent ancestral line. Mosquito transmission did not reverse the increased parasite replication rates that had accrued during serial passage, but it did increase rosetting frequencies. Re-setting of asexual stage genes during the sexual stages of the life cycle, coupled with stochastic sampling of parasites with variable virulence during population bottlenecks, could account for the virulence reductions and increased rosetting induced by mosquito transmission.     

The role of vector control in stopping the transmission of malaria: threats and opportunities

Malaria control, and that of other insect borne diseases such as dengue, is heavily dependent on our ability to control the mosquito populations that transmit these diseases. The major push over the last decade to reduce the global burden of malaria has been driven by the distribution of pyrethroid insecticide-treated bednets and an increase in coverage of indoor residual spraying (IRS). This has reduced malaria deaths by a third. Progress towards the goal of reducing this further is threatened by lack of funding and the selection of drug and insecticide resistance. When malaria control was initially scaled up, there was little pyrethroid resistance in the major vectors, today there is no country in Africa where the vectors remain fully susceptible to pyrethroids. The first pyrethroid resistance mechanisms to be selected produced low-level resistance which had little or no operational significance. More recently, metabolically based resistance has been selected, primarily in West Africa, which in some mosquito populations produces more than 1000-fold resistance. As this spreads the effectiveness of pyrethroid-based bednets and IRS will be compromised. New public health insecticides are not readily available. The pipeline of agrochemical insecticides that can be re-purposed for public health dried up 30 years ago when the target product profile for agricultural insecticides shifted from broad spectrum, stable, contact-acting insecticides to narrow spectrum stomach poisons that could be delivered through the plant. A public–private partnership, the Innovative Vector Control Consortium, was established in 2005 to stimulate the development of new public health pesticides. Nine potential new classes of chemistry are in the pipeline, with the intention of developing three into new insecticides. While this has been successfully achieved, it will still take 6–9 years for new insecticides to reach the market. Careful management of the resistance situation in the interim will be needed if current gains in malaria control are not to be reversed.     

Role of IL6, IL12B and VDR gene polymorphisms in Plasmodium vivax malaria severity,parasitemia and gametocytemia levels in an Amazonian Brazilian population

ObjectiveTo investigate the influence of IL6, IL12B and VDR single nucleotide polymorphisms (SNPs) in uncomplicated Plasmodium vivax infection symptoms intensity, parasitemia and gametocytemia levels in a Brazilian Amazonian population.MethodsA total of 167 malaria patients infected by P. vivax have parasitemia and gametocytemia levels estimated before treatment. Fourteen clinical symptoms were evaluated and included in a principal component analysis to derive a clinical symptom index. Patients were genotyped for IL6-174C > G, IL12B 735T > C, 458A > G, 159A > C, and VDR FokI, TaqI, BsmI SNPs by Taqman 5’ nuclease assays. A General Linear Model analysis of covariance with age, gender, exposure period and infection history and genetic ancestry was performed to investigate the association of genotypes with parasitemia and gametocytemia levels and with a clinical symptom index.ResultsHigher parasitemia levels were observed in IL6-174C carriers (p = 0.02) whereas IL12B CGT haplotype carriers presented lower parasitemia levels (p = 0.008). VDR TaqIC/BsmIA haplotype carriers showed higher gametocyte levels than non-carriers (p = 0.013). Based on the clinical index values the IL6-174C > G polymorphism was associated with malaria severity. The IL6-174C carriers presented a more severe clinical index when compared to GG homozygotes (p = 0.001).ConclusionThe present study suggests that IL6, IL12 and VDR influence severity, parasitemia and gametocytemia clearance in P. vivax infections, and highlights their potential role in malaria immune response in an Amazonian population.     

Combined pyrethroid and carbamate 'two-in-one' treated mosquito nets: field efficacy against pyrethroid-resistant Anopheles gambiae and Culex quinquefasciatus

A new approach is proposed in the treatment of mosquito nets, using a 'two-in-one' combination of pyrethroid and non-pyrethroid insecticides applied to different parts of bednets. The objectives are mainly to overcome certain limitations of pyrethroid-impregnated bednets currently recommended for malaria control purposes. Apart from developing alternatives to pyrethroid dependency, we sought to counteract pyrethroid irritant effects on mosquitoes (excito-repellency) and resistance to pyrethroids. The idea takes advantage of the presumed host-seeking behaviour of mosquitoes confronted by a net draped over a bed, whereby the mosquito may explore the net from the top downwards. Thus, nets could be more effective if treated on the upper part with residual non-irritant insecticide (carbamate or organophosphate) and with a pyrethroid on the lower part. Sequential exposure to different insecticides with distinct modes of action is equivalent to the use of a mixture as a potential method of managing insecticide resistance. We also intended to improve the control of nuisance mosquitoes, especially Culex quinquefasciatus Say (Diptera: Culicidae) that often survive pyrethroids, in order to encourage public compliance with use of insecticide-treated nets (ITNs). Polyester bednets were pretreated with residual pyrethroid (bifenthrin 50 mg/m2 or deltamethrin 25 mg/m2) on the lower half and with carbamate (carbosulfan 300 mg/m2) on the upper half to minimize contact with net users. Unreplicated examples of these 'two-in-one' treated nets were field-tested against wild mosquitoes, in comparison with an untreated net and bednets treated with each insecticide alone, including PermaNet wash-resistant formulation of deltamethrin 50 mg/m2. Overnight tests involved volunteers sleeping under the experimental bednets in verandah-trap huts at Yaokofikro, near Bouaké in C te d'Ivoire, where the main malaria vector Anopheles gambiae Giles, as well as Culex quinquefasciatus Say, are highly resistant to pyrethroids. Efficacy of these ITNs was assessed in the huts by four entomological criteria: deterrency and induced exophily (effects on hut entry and exit), blood-feeding and mortality rates (immediate and delayed). Overall, the best impact was achieved by the bednet treated with carbosulfan alone, followed by 'two-in-one' treatments with carbosulfan plus pyrethroid. Blood-feeding rates were 13% An. gambiae and 17% Cx. quinquefasciatus in huts with untreated nets, but only 3% with carbosulfan ITNs, 7-11% with combined ITN treatment, 6-8% An. gambiae and 12-14% Cx. quinquefasciatus with pyrethroid alone. Mosquitoes that entered the huts were killed sooner by nets with combined treatment than by pyrethroid alone. Mortality-rates in response to ITNs with carbosulfan (alone or combined with pyrethroid) were significantly greater for Cx. quinquefasciatus, but not for An. gambiae, compared to ITNs with only pyrethroid. About 20% of sleepers reported potential side-effects (headache and/or sneezing) from use of ITN treated with carbosulfan alone. Further development of this new 'two-in-one' ITN concept requires a range of investigations (choice of effective products, cost-benefit analysis, safety, etc.) leading to factory production of wash-resistant insecticidal nets treated with complementary insecticides.     

Plasmodium yoelii: experimental evidences for the conserved epitopes between mouse and human malaria parasite, Plasmodium falciparum

Bioinformatic analyses of gene homologues have revealed functionally conserved epitopes between human and rodent malaria parasites. Here, we present experimental evidence for the presence of functionally and antigenically conserved domains between Plasmodium falciparum and Plasmodium yoelii asexual blood-stages. Merozoite released soluble proteins (MRSPs) from both P. falciparum and P. yoelii bound to heterologous mouse or human red blood cells, respectively. The presence of conserved antigenic epitopes between the two species of parasites was evident by the inhibitory effect of antibodies, developed against P. yoelii in convalescent mice, on P. falciparum growth and merozoite reinvasion in vitro. Furthermore, mice immunized with P. falciparum MRSPs were protected from infection by a P. yoelii challenge. These data indicate that different species of Plasmodium contain antigenically conserved interspecies domains, which are immunogenic and, thus constitute a potential novel antigen source for vaccine development and testing using a mouse model.     

1950—2014年广西横县疟疾疫情流行病学分析及Markov模型预测

目的分析横县1950—2014年疟疾疫情监测数据,探讨该时期疟疾流行特点,为今后防控疟疾提供科学依据。方法收集横县1950—2014年疟疾疫情报告数据,应用Excel2007、SPSS18.0和Matlab2016a统计软件分析疟疾疫情的流行特征。用Markov模型对横县2012—2014年疟疾发病率进行预测,并验证预测效果。结果横县1950—2014年共报告疟疾发病数65 259例,年均发病率为119.74/10万。发病率趋势可分为4个阶段,各阶段年均发病率差异有统计学意义(χ2=365 257.034、P<0.05)。其中,1953年疟疾为发病率最高(4 490.14/10万),1996—2014年疟疾发病率则保持在0.77/10万以下,疟疾发病率总体呈下降趋势。2002—2014年无本地疟疾发生,但输入性疟疾病例占比逐步增大(1984—2014年间输入性疟疾病例占疟疾病例总数的93.75%)。同时,Markov模型预测模型用于发病率预测效果良好。结论广西横县经过60多年疟疾防治,原发性疟疾流行已经得到有效控制。但近年出现的输入性疟疾不可忽视,可能造成疟疾死灰复燃,应该把输入性疟疾的流行病学特征作为研究的重点工作。     

A decade of malaria during pregnancy in Brazil: what has been done concerning prevention and management

In Brazil, malaria remains a disease of major epidemiological importance because ofthe high number of cases in the Amazonian Region. Plasmodium spp infections duringpregnancy are a significant public health problem with substantial risks for thepregnant woman, the foetus and the newborn child. In Brazil, the control of malariaduring pregnancy is primarily achieved by prompt and effective treatment of the acuteepisodes. Thus, to assure rapid diagnosis and treatment for pregnant women withmalaria, one of the recommended strategy for low transmission areas by World HealthOrganization and as part of a strategy by the Ministry of Health, the NationalMalaria Control Program has focused on integrative measures with woman andreproductive health. Here, we discuss the approach for the prevention and managementof malaria during pregnancy in Brazil over the last 10 years (2003-2012) usingmorbidity data from Malaria Health Information System. Improving the efficiency andquality of healthcare and education and the consolidation of prevention programmeswill be challenges in the control of malaria during pregnancy in the next decade.     

Retinol supplementation in murine Plasmodium berghei malaria: effects on tissue levels, parasitaemia and lipid peroxidation

Reduced plasma retinol concentrations occur in human malaria but the benefits of supplementation remain uncertain. We assessed the in vivo efficacy of retinol administration, and its effect on lipid peroxidation, in a Plasmodium berghei murine model. Animals received vehicle (n=17) or retinol (i) before P. berghei inoculation (four doses), (ii) at parasitaemia 10-15% (three to four doses) or (iii) before and after inoculation (six to seven doses; n=15 in each group), with euthanasia on day 8 post-inoculation or when the parasitaemia exceeded 50%. Multiple-dose pre-inoculation retinol reduced endpoint parasitaemia by 24% (P=0.001 versus controls). A reduction of 18% (P=0.042) was observed when retinol was given to parasitaemic animals. Retinol was ineffective when given both before and after infection (11% reduction; P=0.47). Although retinol supplementation did not change plasma retinol concentrations, liver retinol content increased and correlated inversely with endpoint parasitaemia (r=-0.45, P=0.001). Malaria infection augmented concentrations of the free radical lipid peroxidation end-product F(2)-isoprostanes in plasma, erythrocytes and liver by 1.8-, 2.8- and 4.9-fold, respectively, but retinol supplementation had no effect on these increases. Consistent with some human malaria studies, prophylactic retinol reduces P. berghei parasitaemia. This effect relates to augmentation of tissue retinol stores rather than to retinol-associated changes in oxidant status.     

Proteomic signature of periodontal disease in pregnancy: Predictive validity for adverse outcomes

The rate of preterm birth is a public health concern worldwide because it is increasing and efforts to prevent it have failed. We report a Clinically Relevant Complex Systematic Review (CSCSR) designed to identify and evaluate the best available evidence in support of the association between periodontal status in women and pregnancy outcome of preterm low birth weight. We hypothesize that the traditional limits of research synthesis must be expanded to incorporate a translational component. As a proof-of-concept model, we propose that this CSCSR can yield greater validity of efficacy and effectiveness through supplementing its recommendations with data of the proteomic signature of periodontal disease in pregnancy, which can contribute to addressing specifically the predictive validity for adverse outcomes. For this CRCSR, systematic reviews were identified through The National Library of MedicinePubmed, The Cochrane library, CINAHL, Google Scholar, Web of Science, and the American Dental Association web library. Independent reviewers quantified the relevance and quality of this literature with R-AMSTAR. Homogeneity and inter-rater reliability testing were supplemented with acceptable sampling analysis. Research synthesis outcomes were analyzed qualitatively toward a Bayesian inference, and converge to demonstrate a definite association between maternal periodontal disease and pregnancy outcome. This CRCSR limits heterogeneity in terms of periodontal disease, outcome measure, selection bias, uncontrolled confounders and effect modifiers. Taken together, the translational CRCSR model we propose suggests that further research is advocated to explore the fundamental mechanisms underlying this association, from a molecular and proteomic perspective.     

Prophylactic effect of vitamin E against hepatotoxicity,nephrotoxicity, haematological indices and histopathology induced by diazinon insecticide in mice

Considering that the involvement of reactive oxygen species(ROS)has been implicated in the toxicity of various pesticides,this study was designed to study the ameliorative effect of Vitamin E(100 mg/kg body weight)on mice(25-30 mg)treated with diazinon(32.5 or 16.25 mg/kg body weight)organophosphate insecticide for 14 days.Subchronic DZN exposure and the protective effects of vitamins E(vitE)were evaluated for their effects on haematological indices,the enzymes concerning liver damage [plasma alanine aminot...     

Responses of Anopheles culicifacies sibling species A and B to DDT and HCH in India: implications in malaria control

Differential responses of Anopheles culicifacies Giles sibling species A and B to DDT were evident from higher survival rate of species B in laboratory bioassays and greater proportions of species B in DDT-sprayed villages of northern India, compared with those under HCH pressure. Both species A and B have become almost completely resistant to HCH in this area due to regular house-spraying with HCH for about the last 10 years. Because species A predominates in northern India, where it has been incriminated as an important vector of malaria, and species A is more susceptible than species B to DDT, it is suggested that DDT would control malaria transmission more effectively than HCH in this situation. Monitoring of insecticide resistance in species A is therefore recommended as the basis for future choice of insecticides to be used by the National Malaria Eradication Programme.     

Susceptibility of cell substrates to PrPSc infection and safety control measures related to biological and biotherapeutical products

Concerns over the potential for infectious prion proteins to contaminate human biologics and biotherapeutics have been raised from time to time. Transmission of the pathogenic form of prion protein (PrPSc) through veterinary vaccines has been observed, yet no human case through the use of vaccine products has been reported. However, iatrogenic transmissions of PrPSc in humans through blood components, tissues, and growth hormone have been reported. These findings underscore the importance of reliable detection or diagnostic methods to prevent the transmission of prion diseases, given that the number of asymptomatic infected individuals remains unknown, the perceived incubation time for human prion diseases could be decades, and no cure of the diseases has been found yet. A variety of biochemical and molecular methods can selectively concentrate PrPSc to facilitate its detection in tissues and cells. Furthermore, some methods routinely used in the manufacturing process of biological products have been found to be effective in reducing PrPSc from the products. Questions remain unanswered as to the validation criteria of these methods, the minimal infectious dose of the PrPSc required to cause infection and the susceptibility of cells used in gene therapy or the manufacturing process of biological products to PrPSc infections. Here, we discuss some of these challenging issues.     

An integrated model of thermodynamic-hemodynamic-pharmacokinetic system and its application on decoupling control of intracranial temperature and pressure in brain hypothermia treatment

Brain hypothermia treatment (BHT) is an intensive care characterized by simultaneous managements of various vital signs, such as intracranial temperature (ICT) and pressure (ICP), of the severe neuropatient. Medical treatments including therapeutic ambient cooling and diuresis are separately carried out based on the experience of the medical staff involved in the clinical management of various pathophysiological processes, such as thermodynamics, hemodynamics and pharmacokinetics. However, no special attention has been paid to the interactions among these subsystems in therapeutic hypothermia because of the lack of theoretical knowledge. Therefore, quantitative analyses using an integrated model of various physiological processes and their interactions are of pressing need. In the present paper, we propose a general compartmental model to describe the pathophysiological processes of the three aforementioned dynamics, on account of the dynamical analogy of temperature, pressure and concentration. The model is verified by the agreement of model-based simulation results with clinical evidence. Based on responses of the integrated model to various stimuli, a transfer function matrix is identified to linearly approximate the characteristic interrelationships between medical treatments (ambient cooling and diuresis) and the vital signs (ICT and ICP). Then a controller that decouples ambient cooling and diuresis is proposed for efficient management of ICT and ICP, enhancement of hypothermic decompression and reduction of diuretic dosage. Decoupling control simulation indicates that ICT and ICP of the integrated model, representing a patient under BHT, can be simultaneously regulated by a single PID controller for ambient cooling and another for diuresis. The proposed decoupler effectively establishes hypothermic decompression, reduces the dosage of diuretic and improves ICP management. Theoretical analyses of the integrated model and decoupling control of ICT and ICP provide insights into the intensive care of various pathophysiological processes in patients undergoing BHT.     

Use of fluorometry for monitoring and control of a bioreactor

A new fluorescent bioreactor monitoring probe-multiple excitation fluorometric system (MEFS)-has been developed. This probe was compared to the commercially available BioChem Technology FluroMeasure system (NADH probe). In this task the fluorescence behavior of three model fermentation systems, ethanol fermentation by Candida utilis, phenol fermentation by Pseudomonas putida, and glucose fermentation by Saccharomyces cerevisiae, were examined. The results indicated that the fluorescence intensity and behavior of various cellular fluorophors vary significantly between the different fermentation systems. Monitoring a fermentation process using only NAD(P)H fluorescence provided limited information. The NAD(P)H fluorescence was found not to be the best fluorescence signal for monitoring cell concentrations. The best way of monitoring a bioreactor by fluorometry may be to monitor several fluorophors in the whole culture broth simultaneously and to relate these fluorescence signals to various biological parameters.     

防虫网对韭菜迟眼蕈蚊隔离效果和对韭菜生长的影响

【目的】为了指导田间正确使用防虫网控制韭菜迟眼蕈蚊Bradysia odoriphaga,本文明确了防虫网对成虫的隔离作用和对韭菜生长的影响。【方法】实验室内测定了韭菜迟眼蕈蚊成虫在不同目数防虫网制成的笼内48 h的逃出率,并通过连续3年的田间小区试验明确防虫网对韭菜迟眼蕈蚊的控制效果。同时,通过田间单墩韭菜笼罩和小区试验验证不同目数防虫网对韭菜生长的影响。【结果】随着防虫网目数的增大,韭菜迟眼蕈蚊雌雄成虫逃出率的逐渐降低,20目网袋内雌雄成虫的逃出率接近100%,40~80目网袋内的逃出率在5%~60%之间,100目和120目网袋内逃出率接近0。田间试验证明80目对韭菜迟眼蕈蚊的阻隔效果最好(P<0.05),60目阻隔效果效果优于40目,但差异不显著(P>0.05)。田间单墩韭菜笼罩试验发现防虫网目数大于70目不利于韭菜生长,40目、50目、60目防虫网在干燥季节促进韭菜生长,小区试验进一步验证了80目对韭菜生长不利,40目和60目对韭菜生长无影响或促进韭菜生长。【结论】40~60目对韭菜迟眼蕈蚊的控制效果较好。     

The incidence and severity of Jatropha dieback disease in Zaria,Nigeria

A survey was conducted on Jatropha plantations within Zaria to assess disease incidence and severity on two fields along Shika road and near the dam (Irrigation site) of the Institute for Agricultural Research (IAR) at Samaru and a plantation of the National Research Institute for Chemical Technology (NARICT) at Basawa. An assessment of incidence and severity of the disease was done on six accessions collected from four Local Government Areas (Giwa, B/Gwari, Soba, Lere) of Kaduna state and grown in one of the I.A.R fields along Bomo road at Samaru. The accessions were collected from Gangara, Maidaro, Farin Gida (Giwa LGA), Birnin Gwari (B/Gwari LGA), Kayarda (Lere LGA) and Soba (Soba LGA). The causal organism of dieback on Jaropha curcas L, was isolated and its pathogenicity determined. The isolated Fusarium sp. incited dieback/stem-rot disease when inoculated on healthy Jatropha seedlings. The disease incidence was significantly higher on NARICT plantation compared to the two IAR fields which were not significantly different from each other. The accessions from Gangara, Kayarda, Birnin Gwari and Soba did not significantly differ from each other but had significantly higher disease incidence than those from Maidaro and Farin Gida. Accession from Soba had significantly higher disease severity compared to the accessions from all the other LGAs, which did not differ statistically from each other.