The proliferation of artificial container habitats in urban areas has benefitted urban adaptable mosquito species globally. In areas where mosquitoes transmit viruses and parasites, it can promote vector population productivity and fuel mosquito-borne disease outbreaks. In Britain, storage of water in garden water butts is increasing, potentially expanding mosquito larval habitats and influencing population dynamics and mosquito-human contact. [Read more…]
Wolbachia Infection Modifies the Profile, Shuttling and Structure of MicroRNAs in a Mosquito Cell Line
MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in many biological processes such as development, cell signaling and immune response. Small RNA deep sequencing technology provided an opportunity for a thorough survey of the miRNA profile of a mosquito cell line from Aedes aegypti. We characterized the miRNA composition of the nucleus and the cytoplasm of uninfected cells and compared it with the one of cells infected with the endosymbiotic bacterium Wolbachia strain wMelPop-CLA. We found an overall increase of small RNAs between 18 and 28 nucleotides in both cellular compartments in Wolbachia-infected cells and identified specific miRNAs induced and/or suppressed by the Wolbachia infection. We discuss the mechanisms that the cell may use to shuttle miRNAs between the cytoplasm and the nucleus. In addition, we identified piRNAs that changed their abundance in response to Wolbachia infection. The miRNAs and piRNAs identified in this study provide promising leads for investigations into the host-endosymbiont interactions and for better understanding of how Wolbachia manipulates the host miRNA machinery in order to facilitate its persistent replication in infected cells.
Citation: Mayoral JG, Etebari K, Hussain M, Khromykh AA, Asgari S (2014) Wolbachia Infection Modifies the Profile, Shuttling and Structure of MicroRNAs in a Mosquito Cell Line. PLoS ONE 9(4): e96107. doi:10.1371/journal.pone.0096107
Copyright: © 2014 Mayoral et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
IgG1 and IgG4 Antibody Responses to the Anopheles gambiae Salivary Protein gSG6
Human antibody response to the Anopheles gambiae salivary protein gSG6 has recently emerged as a potentially useful tool for malaria epidemiological studies and for the evaluation of vector control interventions. However, the current understanding of the host immune response to mosquito salivary proteins and of the possible crosstalk with early response to Plasmodium parasites is still very limited. We report here the analysis of IgG1 and IgG4 subclasses among anti-gSG6 IgG responders belonging to Mossi and Fulani from Burkina Faso, two ethnic groups which are known for their differential humoral response to parasite antigens and for their different susceptibility to malaria. The IgG1 antibody response against the gSG6 protein was comparable in the two groups. On the contrary, IgG4 titers were significantly higher in the Fulani where, in addition, anti-gSG6 IgG4 antibodies appeared in younger children and the ratio IgG4/IgG1 stayed relatively stable throughout adulthood. Both gSG6-specific IgG1 and IgG4 antibodies showed a tendency to decrease with age whereas, as expected, the IgG response to the Plasmodium circumsporozoite protein (CSP) exhibited an opposite trend in the same individuals. These observations are in line with the idea that the An. gambiae gSG6 salivary protein induces immune tolerance, especially after intense and prolonged exposure as is the case for the area under study, suggesting that gSG6 may trigger in exposed individuals a Th2-oriented immune response.
Citation: Rizzo C, Ronca R, Lombardo F, Mangano V, Sirima SB, et al. (2014) IgG1 and IgG4 Antibody Responses to the Anopheles gambiae Salivary Protein gSG6 in the Sympatric Ethnic Groups Mossi and Fulani in a Malaria Hyperhendemic Area of Burkina Faso. PLoS ONE 9(4): e96130. doi:10.1371/journal.pone.0096130
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Targeting NAD+ Metabolism in the Human Malaria Parasite Plasmodium falciparum
Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite utilized as a redox cofactor and enzyme substrate in numerous cellular processes. Elevated NAD+ levels have been observed in red blood cells infected with the malaria parasite Plasmodium falciparum, but little is known regarding how the parasite generates NAD+. Here, we employed a mass spectrometry-based metabolomic approach to confirm that P. falciparum lacks the ability to synthesize NAD+ de novo and is reliant on the uptake of exogenous niacin. [Read more…]
Diagnostic Testing of Pediatric Fevers: Meta-Analysis of 13 National Surveys Assessing Influences of Malaria Endemicity and Source of Care on Test Uptake for Febrile Children under Five Years
In 2010, the World Health Organization revised guidelines to recommend diagnosis of all suspected malaria cases prior to treatment. There has been no systematic assessment of malaria test uptake for pediatric fevers at the population level as countries start implementing guidelines. We examined test use for pediatric fevers in relation to malaria endemicity and treatment-seeking behavior in multiple sub-Saharan African countries in initial years of implementation. [Read more…]
Dihydroartemisinin-Piperaquine vs. Artemether-Lumefantrine for First-Line Treatment of Uncomplicated Malaria in African Children: A Cost-Effectiveness Analysis
Recent multi-centre trials showed that dihydroartemisinin-piperaquine (DP) was as efficacious and safe as artemether-lumefantrine (AL) for treatment of young children with uncomplicated P. falciparum malaria across diverse transmission settings in Africa. Longitudinal follow-up of patients in these trials supported previous findings that DP had a longer post-treatment prophylactic effect than AL, reducing the risk of reinfection and conferring additional health benefits to patients, particularly in areas with moderate to high malaria transmission. [Read more…]
Non-Profit Offers Free Kits of Potential Malaria Cures for Researchers to Study
A nonprofit called Medicines for Malaria Venture (MMV) is sending free kits of potential malaria cures for researchers. It’s called The Malaria Box, and it is the result of a high-throughput screen done by MMV and cooperating pharmaceutical companies. All you have to do is send your request, along with a summary of your research and how you plan to share the data. The box contain samples of 400 substances that MMV has found may be promising malaria cures. The Malaria Box is meant to be a starting point for researchers at universities or small companies.
Available free of charge, on request, the Malaria Box is a treasure trove of 400 diverse compounds with antimalarial activity. The Malaria Box has been assembled by MMV in a bid to catalyse malaria and neglected disease drug discovery and research. All of the compounds have confirmed activity against the blood-stage of P. falciparum and are commercially available. It includes:
- 200 diverse drug-like compounds as starting points for oral drug discovery and development
- 200 diverse probe-like compounds for use as biological tools in malaria research
The final selection, formatted as solutions at 10mM concentration in dimethyl sulfoxide, was distilled from around 20,000 hits generated from an extensive screening campaign of around four million compounds from the libraries of St. Jude Children’s Research Hospital, TN, USA, Novartis and GSK. The selection was made to provide the broadest cross-section of structural diversity and, in the case of the drug-like compounds, properties commensurate with oral absorption and the minimum presence of toxicophores.
All that is asked in return of Malaria Box users is for the resulting data to be published and placed in the public domain to help continue the virtuous cycle of research.
More information Medicines for Malaria Venture.
Mass drug administration for the control and elimination of Plasmodium vivax malaria: an ecological study from Jiangsu province, China
Recent progress in malaria control has caused renewed interest in mass drug administration (MDA) as a potential elimination strategy but the evidence base is limited. China has extensive experience with MDA, but it is not well documented.
Methods
An ecological study was conducted to describe the use of MDA for the control and elimination of Plasmodium vivax in Jiangsu Province and explore the association between MDA and malaria incidence. Two periods were focused on: 1973 to 1983 when malaria burden was high and MDA administered to highly endemic counties province-wide, and 2000 to 2009, when malaria burden was low and a focal approach was used in two counties. All available data about the strategies implemented, MDA coverage, co-interventions, incidence, and adverse events were collected and described. Joinpoint analysis was used to describe trends in incidence and the relationship between MDA coverage and incidence was explored in negative binomial regression models.
Results
From 1973 to 1983, MDA with pyrimethamine and primaquine was used on a large scale, with up to 30 million people in target counties covered in a peak year (50% of the total population). Joinpoint analyses identified declines in annual incidence, -56.7% (95% CI -75.5 to -23.7%) from 1973–1976 and -12.4% (95% CI -24.7 to 2.0%) from 1976–1983. Population average negative binomial models identified a relationship between higher total population MDA coverage and lower monthly incidence from 1973–1976, IRR 0.98 (95% CI 0.97 to 1.00), while co-interventions, rainfall and GDP were not associated. From 2000–2009, incidence in two counties declined (annual change -43.7 to -14.0%) during a time when focal MDA using chloroquine and primaquine was targeted to villages and/or individuals residing near passively detected index cases (median 0.04% of total population). Although safety data were not collected systematically, there were rare reports of serious but non-fatal events.
Conclusions
In Jiangsu Province, China, large-scale MDA was implemented and associated with declines in high P. vivax malaria transmission; a more recent focal approach may have contributed to interruption of transmission. MDA should be considered a potential key strategy for malaria control and elimination.
AUTHORS: Michelle S Hsiang, Jimee Hwang, Amy R Tao, Yaobao Liu, Adam Bennett, George Dennis Shanks, Jun Cao, Stephen Patrick Kachur, Richard GA Feachem, Roly D Gosling and Qi Gao
Source: Malaria Journal 2013, 12:383 doi:10.1186/1475-2875-12-383
http://www.malariajournal.com/content/12/1/383/abstract
Published: 1 November 2013
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Effect of Iron Supplements On Children Living in Malaria-Endemic Areas
Children in a malaria-endemic community in Ghana who received a micronutrient powder with iron did not have an increased incidence of malaria, according to a study in the September 4 issue of JAMA. Previous research has suggested that iron supplementation for children with iron deficiency in malaria-endemic areas may increase the risk of malaria.
“In sub-Saharan Africa, malaria is a leading cause of childhood morbidity and mortality, and iron deficiency is among the most prevalent preventable nutritional deficiencies. The provision of iron to children with iron deficiency anemia can enhance motor and cognitive development and reduce the prevalence of severe anemia. However, studies have suggested that iron deficiency anemia may offer protection against malaria infection and that the provision of iron may increase malaria morbidity and mortality,” according to background information in the article. “In 2006, the World Health Organization and the United Nations Children’s Fund released a joint statement that recommended limiting use of iron supplements (tablets or liquids) among children in malaria-endemic areas because of concern about increased malaria risk. As a result, anemia control programs were either not initiated or stopped in these areas.”
Stanley Zlotkin, M.D., Ph.D., of the Hospital for Sick Children, Toronto, and colleagues conducted a study to determine the effect of providing micronutrient powder (MNP) with or without iron on the incidence of malaria among children living in a high malaria-burden area. The randomized trial, which included children 6 to 35 months of age (n = 1,958 living in 1,552 clusters), was conducted over 6 months in 2010 in a rural community setting in central Ghana, West Africa. A cluster was defined as a compound including 1 or more households. Children were excluded if iron supplement use occurred within the past 6 months, they had severe anemia, or severe wasting. Children were randomized by cluster to receive a MNP with or without iron for 5 months followed by 1-month of further monitoring. Insecticide-treated bed nets were provided at enrollment, as well as malaria treatment when indicated.
Throughout the intervention period, adherence to the use of MNP and insecticide-treated bed nets were similar between the iron group and the no iron group. The researchers found that the overall incidence of malaria was lower in the iron group compared with the no iron group, but after adjustment for baseline values for iron deficiency and moderate anemia, these differences were no longer statistically significant. “Similar associations were found during the 5-month intervention period only for both malaria and malaria with parasite counts greater than 5000/µL (severe malaria). A secondary analysis demonstrated that malaria risk was reduced among the subgroup of those in the iron group who had iron deficiency and anemia at baseline.”
Overall, hospital admission rates did not differ significantly between groups. However, during the 5-month intervention period, there were more children admitted to the hospital in the iron group vs. the no iron group (156 vs. 128, respectively).
“The findings from the current study not only address a gap in the literature, but also have potentially important policy implications for countries like Ghana that have not implemented iron supplementation or fortification as part of anemia control programs in part due to the joint recommendation from the WHO and UNICEF. For ethical reasons, we ensured that all participants were not denied existing malaria prevention (insecticide-treated bed nets) or malaria treatment. As such, our results most likely can be applied to other malaria-endemic settings in which similar malaria control measures are in place. Overall, given our findings and the new WHO guidelines recommending iron fortification for the prevention and treatment of anemia among children younger than 2 years (in whom the prevalence of anemia is ≥20 percent), there should be renewed interest and consideration for implementing iron fortification in Ghana as part of the national nutrition policy.”
Editorial: Iron Fortification and Malaria Risk in Children
In an accompanying editorial, Andrew M. Prentice, Ph.D., of the London School of Hygiene and Tropical Medicine, and colleagues write that the increase seen in this study in hospital admissions among the iron supplementation group, which by definition constitutes a potentially serious adverse event, adds to the concerns about the safety of iron administration in highly malaria-endemic environments.
“Participants in an expert panel convened by the World Health Organization in 2007 speculated that iron given with foods, either by centralized or point-of-use fortification, would be safe. However, the Ghanaian trial reported by Zlotkin et al in this issue of JAMA now becomes the fourth trial to question this suggestion, and leaves global health policy makers with an unresolved dilemma. Until a means of safely administering iron in infectious environments has been developed, there remains an imperative to reduce the infectious burden as a prerequisite to moving poor populations from their current state of widespread iron deficiency and anemia.”
Source: American Medical Association (AMA)
Malaria Infected Mosquitoes Attracted to Human Odor
Abstract
There is much evidence that some pathogens manipulate the behaviour of their mosquito hosts to enhance pathogen transmission. However, it is unknown whether this phenomenon exists in the interaction of Anopheles gambiae sensu stricto with the malaria parasite, Plasmodium falciparum – one of the most important interactions in the context of humanity, with malaria causing over 200 million human cases and over 770 thousand deaths each year.
Here we demonstrate, for the first time, that infection with P. falciparum causes alterations in behavioural responses to host-derived olfactory stimuli in host-seeking female An. gambiae s.s. mosquitoes. In behavioural experiments we showed that P. falciparum-infected An. gambiae mosquitoes were significantly more attracted to human odors than uninfected mosquitoes. Both P. falciparum-infected and uninfected mosquitoes landed significantly more on a substrate emanating human skin odor compared to a clean substrate. However, significantly more infected mosquitoes landed and probed on a substrate emanating human skin odor than uninfected mosquitoes. [Read more…]
- 1
- 2
- 3
- …
- 5
- Next Page»