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MJ Blackman et al. Recent insights into apicomplexan parasite egress provide new views to a kill. Curr Opin Microbiol
A hallmark of apicomplexan pathogens such as Plasmodium, Toxoplasma and Cryptosporidium is that they invade, replicate within, and then egress from their host cells. . . .
pLDH level of clinically isolated Plasmodium vivax and detection limit of pLDH based malaria rapid diagnostic test
Background: The malaria rapid diagnostic tests (RDTs) are now widely used in the world. Compared to Plasmodium falciparum, a poor sensitivity of RDTs was reported against Plasmodium vivax based on the adopted antibody against pan-Plasmodium antigen lactate dehydrogenase (pLDH) or aldolase. Levels of pLDH were measured from patient with P. vivax, and the correlations between the levels of pLDH and the sensitivities of RDTs were analysed among Republic of Korea (ROK) isolates. Methods: Three RDTs, OptiMAL test, SD BIOLINE Malaria Ag P.f/Pan test, Humasis Malaria Pf/Pan antigen test, and the Genedia pLDH antigen ELISA were performed with blood samples from 152 febrile patients and 100 healthy controls. Results: Three malaria RDTs revealed sensitivities between 85.5 (131/152) and 86.8% (132/152) with highest sensitivity for the detection of P.vivax by pLDH antigen ELISA test (145/152, 95.4%) in comparison to traditional microscopy using Giemsa--stained slides. None of the healthy control tested positive by three RDTs or ELISA, indicating 100% specificity in their respective test. Levels of pLDH among Korean P. vivax isolates ranged between 0 ng/mL and 22,387.2 ng/mL (mean +/- standard deviation 3,917.5 +/- 6,120.9 ng/mL). The lower detection limits of three RDTs were between 25 and 50 ng/mL with artificially diluted samples. The moderate degree of correlation was observed between parasitaemia and concentrations of pLDH (r = 0.4, p < 0.05). Conclusion: The pLDH levels of P. vivax are the main explanation for the variations in the performance of pLDH-based RDTs. Therefore, comparing sensitivities of RDT may need to include targeted biomarker value of patients.
Background: Simian malaria is still an open question concerning the species of Plasmodium parasites and species of New World monkeys susceptible to the parasites. In addition, the lingering question as to whether these animals are reservoirs for human malaria might become important especially in a scenario of eradication of the disease. To aid in the answers to these questions, monkeys were surveyed for malaria parasite natural infection in the Amazonian state of Rondonia, Brazil, a state with intense environmental alterations due to human activities, which facilitated sampling of the animals. Methods: Parasites were detected and identified in DNA from blood of monkeys, by PCR with primers for the 18S rRNA, CSP and MSP1 genes and sequencing of the amplified fragments. Multiplex PCR primers for the 18S rRNA genes were designed for the parasite species Plasmodium falciparum and Plasmodium vivax, Plasmodium malariae/Plasmodium brasilianum and Plasmodium simium. Results: An overall infection rate of 10.9% was observed or 20 out 184 monkey specimens surveyed, mostly by P. brasilianum. However, four specimens of monkeys were found infected with P. falciparum, two of them doubly infected with P. brasilianum and P. falciparum. In addition, a species of monkey of the family Aotidae, Aotus nigriceps, is firstly reported here naturally infected with P. brasilianum. None of the monkeys surveyed was found infected with P. simium/P. vivax. Conclusion: The rate of natural Plasmodium infection in monkeys in the Brazilian state of Rondonia is in line with previous surveys of simian malaria in the Amazon region. The fact that a monkey species was found that had not previously been described to harbour malaria parasites indicates that the list of monkey species susceptible to Plasmodium infection is yet to be completed. Furthermore, finding monkeys in the region infected with P. falciparum clearly indicates parasite transfer from humans to the animals. Whether this parasite can be transferred back to humans and how persistent the parasite is in monkeys in the wild so to be efficient reservoirs of the disease, is yet to be evaluated. Finding different species of monkeys infected with this parasite species suggests indeed that these animals can act as reservoirs of human malaria.
Background: The biting behaviour of mosquitoes is crucial for the transmission of malaria parasites. This study focuses on the feeding behaviour of Culex pipiens mosquitoes with regard to the infection status by the avian malaria parasite Plasmodium relictum (lineage SGS1). Methods: Uninfected and sporozoite-infected mosquitoes were provided with a choice between an uninfected bird and a bird undergoing a chronic P. relictum infection. Mosquito choice is assessed by microsatellite typing of the ingested blood. Results: Chronically infected birds are more attractive to mosquitoes. This choice is not altered by the infection status of the mosquitoes: both infected and uninfected mosquitoes have similar host choice behaviours and are more attracted towards infected birds. Conclusions: These results support some, but not all predictions derived from the hypothesis that malaria parasites can manipulate the behaviour of their mosquito vectors to enhance their transmission. The possible mechanisms driving this manipulation, the evolutionary dynamics leading to the modification of the biting behaviour of mosquitoes by Plasmodium sp. as well as the implications for malaria epidemiology are discussed.
In a report to be released this month, the Promoting Malaria Prevention and Treatment Project will describe an innovative model for distributing over 12 million mosquito nets to prevent the transmission of malaria in Ghana.
WC Koff et al. Accelerating next-generation vaccine development for global disease prevention. Science
Vaccines are among the greatest successes in the history of public health. . . .
Background: Plasmodium vivax and Plasmodium falciparum cause a significant illness burden in Peru. Anopheline indices for populated communities in the peri-Iquitos region of Loreto have been reported to be remarkably low, with entomological inoculation rates (EIR) estimated at one to 30 infectious bite per year based on a few studies in close proximity to the urban centre of Iquitos and surrounding deforested areas. Local reports suggest that a large number of the reported cases are contracted outside of populated communities in undeveloped riverine areas frequented by loggers and fishermen. Methods: To better understand vectorial capacity in suspected high malaria transmission zones in a rural district near Iquitos, Peru, mosquito collections were conducted at different points in the seasonality of malaria transmission in 21 sites frequented by occupational labourers. Prevalence of Plasmodium spp in vectors was determined by circumsporozoite protein ELISA on individual mosquitoes. Slide surveillance was performed for humans encountered in the zone. Results: In total, of 8,365 adult female mosquitoes examined, 98.5% were identified as Anopheles darlingi and 117 (1.4%) tested positive for sporozoites (P. falciparum, P. vivax V-210 or P. vivax V247). Measured human biting rates at these sites ranged from 0.102 to 41.13 bites per person per hour, with EIR values as high as 5.3 infective bites per person per night. Six percent of the 284 blood films were positive for P. vivax or P. falciparum; however 88% of the individuals found to be positive were asymptomatic at the time of sampling. Conclusions: The results of this study provide key missing indices of prominent spatial and temporal heterogeneity of vectorial capacity in the Amazon Basin of Peru. The identification of a target human subpopulation as a principal reservoir and dispersion source of Plasmodium species has important implications for vaccine development and the delivery of effective targeted malaria control strategies.
Activation of minority-variant Plasmodium vivax hypnozoites following artesunate + amodiaquine treatment in a 23-year old man with relapsing malaria in Antananarivo, Madagascar
In endemic areas, Plasmodium vivax relapses are difficult to distinguish from new infections. Genotyping of patients who experience relapse after returning to a malaria-free area can be used to explore the nature of hypnozoite activation and relapse. This paper describes a person who developed P. vivax malaria for the first time after travelling to Boriziny in the malaria endemic coastal area of Madagascar, then suffered two P. vivax relapses 11 weeks and 21 weeks later despite remaining in Antananarivo in the malaria-free central highlands area. He was treated with the combination artesunate + amodiaquine according to the national malaria policy in Madagascar. Genotyping by PCR-RFLP at pvmsp-3alpha as well as pvmsp1 heteroduplex tracking assay (HTA) showed the same dominant genotype at each relapse. Multiple recurring minority variants were also detected at each relapse, highlighting the propensity for multiple hypnozoite clones to activate simultaneously to cause relapse.
Background: Falciparum malaria increases the risk for bacteraemia, whereas the relationship between vivax malaria and bacteraemia is not clear. Data from a prospective fever surveillance study in Kolkata, India were reanalysed for the potential association between Plasmodium vivax malaria and bacteraemia. Methods: Patients of all ages presenting with fever of three days or more to a project health outpost were invited to participate. A blood film and blood culture was performed on presentation. Treatment and referral were provided according to national guidelines. The case fraction and incidence of malaria, bacteraemia, and co-infection were calculated. Results: 3,371 participants were enrolled during a one-year study period, of whom 93/3,371 (3%) had malaria (89/93 [96%] Plasmodium vivax) and 256 (7.6%) bacteraemia. There were 154 malaria, 423 bacteraemia and 10 P. vivax-bacteremia coinfection episodes per 100,000/year. Among the malaria-bacteraemia co-infections, all were vivax malaria and 5/6 (83%) bacteria isolated were gram-negative (one S. Typhi, one S. Paratyphi A, three other Gram negative). Bacteraemia occurred in 6/89 (6.7% [95%CI: 3.1-13.9%]) of P. vivax cases versus 250/3,278 (7.6% [95% CI: 6.7-8.6%]) without Plasmodium infection (p=0.76). Conclusions: While an increased risk was not demonstrated, concomitant bacteraemia occurs frequently in vivax malaria in an area with a high background incidence of bacteraemia, and should be considered in cases of vivax malaria with severe manifestations.
Health care seeking patterns and determinants of out-of-pocket expenditure for Malaria for the children under-five in Uganda
Background: The objectives of this study were to assess the patterns of treatment seeking behaviour for children under five with malaria; and to examine the statistical relationship between out-of-pocket expenditure (OOP) on malaria treatment for under-fives and source of treatment, place of residence, education and wealth characteristics of Uganda households. OOP expenditure on health care is now a development concern due to its negative effect on households' ability to finance consumption of other basic needs. Methods: The 2009 Uganda Malaria Indicator Survey was the source of data on treatment seeking behaviour for under-five children with malaria, and patterns and levels of OOP expenditure for malaria treatment. Binomial logit and Log-lin regression models were estimated. In logit model the dependent variable was a dummy (1=incurred some OOP, 0=none incurred) and independent variables were wealth quintiles, rural versus urban, place of treatment, education level, sub-region, and normal duty disruption. The dependent variable in Log-lin model was natural logarithm of OOP and the independent variables were the same as mentioned above. Results: Five key descriptive analysis findings emerge. First, malaria is quite prevalent at 44.7% among children below the age of five. Second, a significant proportion seeks treatment (81.8 %). Third, private providers are the preferred option for the under-fives for the treatment of malaria. Fourth, the majority pay about 70.9% for either consultation, medicines, transport or hospitalization but the biggest percent of those who pay, do so for medicines (54.0%). Fifth, hospitalization is the most expensive at an average expenditure of US$7.6 per child, even though only 2.9% of those that seek treatment are hospitalized.The binomial logit model slope coefficients for the variables richest wealth quintile, Private facility as first source of treatment, and sub-regions Central 2, East central, Mid-eastern, Mid-western, and Normal duties disrupted were positive and statistically significant at 99% level of confidence. On the other hand, the Log-lin model slope coefficients for Traditional healer, Sought treatment from one source, Primary educational level, North East, Mid Northern and West Nile variables had a negative sign and were statistically significant at 95% level of confidence. Conclusion: The fact that OOP expenditure is still prevalent and private provider is the preferred choice, increasing public provision may not be the sole answer. Plans to improve malaria treatment should explicitly incorporate efforts to protect households from high OOP expenditures. This calls for provision of subsidies to enable the private sector to reduce prices, regulation of prices of malaria medicines, and reduction/removal of import duties on such medicines.
Taking an image of an individual molecule while it undergoes a chemical reaction has been deemed one of the holy grails of chemistry. Scientists at the University of Berkeley and the University of the Basque Country have managed, for the very first time,
Rapid expansion of programs to prevent HIV transmission to babies and vaccinate children show how results can be achieved in relatively little time. Some of the world's poorest countries have managed to cut maternal and young child mortality rates by half
Defining mechanisms by which Plasmodium virulence is regulated is central to understanding the pathogenesis of human malaria. . . .
Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator's product
Background: Existence of anti-malarial generic drugs with low bioavailability marketed on sub-Saharan Africa has raised a concern on patients achieving therapeutic concentrations after intake of these products. This work compared bioavailability of one generic tablet formulation with innovator's product. Both were fixed dose combination tablet formulations containing artemether and lumefantrine.MethodologyThe study was conducted in Dar Es Salaam, Tanzania, in which a survey of the most abundant generic containing artemether-lumefantrine tablet formulation was carried out in retail pharmacies. The most widely available generic (Artefan(R), Ajanta Pharma Ltd, Maharashtra, India) was sampled for bioavailability comparison with Coartem(R) (Novartis Pharma, Basel, Switzerland) - the innovator's product. A randomized, two-treatment cross-over study was conducted in 18 healthy Tanzanian black male volunteers. Each volunteer received Artefan(R) (test) and Coartem(R) (as reference) formulation separated by 42 days of drug-free washout period. Serial blood samples were collected up to 168 hours after oral administration of a single dose of each treatment. Quantitation of lumefantrine plasma levels was done using HPLC with UV detection. Bioequivalence of the two products was assessed in accordance with the US Food and Drug Authority (FDA) guidelines. Results: The most widely available generic in pharmacies was Artefan(R) from India. All eighteen enrolled volunteers completed the study and both test and reference tablet formulations were well tolerated. It was possible to quantify lumefantrine alone, therefore, the pharmacokinetic parameters reported herein are for lumefantrine. The geometric mean ratios for Cmax, AUC0-t and AUC0-[infinity] were 84% in all cases and within FDA recommended bioequivalence limits of 80% -- 125%, but the 90% confidence intervals were outside FDA recommended limits (CI 49--143%, 53 - 137%, 52 - 135% respectively). There were no statistical significant differences between the two formulations with regard to PK parameters (P > 0.05). Conclusions: Although the ratios of AUCs and Cmax were within the acceptable FDA range, bioequivalence between Artefan(R) and Coartem(R) tablet formulations was not demonstrated due to failure to comply with the FDA 90 % confidence interval criteria. Based on the observed total drug exposure (AUCs), Artefan(R) is likely to produce a similar therapeutic response as Coartem(R).
E Chen et al. Structural and Functional Basis for Inhibition of Erythrocyte Invasion by Antibodies that Target Plasmodium falciparum EBA-175. PLoS Pathog
Disrupting erythrocyte invasion by Plasmodium falciparum is an attractive approach to combat malaria. . . .