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Prevalence And Risk Factors For Asymptomatic Malaria And Genotyping Of Glucose 6-Phosphate (G6pd) Deficiencies In A Vivax-Predominant Setting, Lao Pdr: Implications For Sub-National Elimination Goals, Andrew A. Lover, Emily Dantzer, Bouasy Hongvanthong, Keobouphaphone Chindavongsa, Susie Welty, Tania Reza, Nimol Khim, Didier Menard, Adam Bennett Dec 2017

Prevalence And Risk Factors For Asymptomatic Malaria And Genotyping Of Glucose 6-Phosphate (G6pd) Deficiencies In A Vivax-Predominant Setting, Lao Pdr: Implications For Sub-National Elimination Goals, Andrew A. Lover, Emily Dantzer, Bouasy Hongvanthong, Keobouphaphone Chindavongsa, Susie Welty, Tania Reza, Nimol Khim, Didier Menard, Adam Bennett

Andrew Lover

Background
Lao People Democratic Republic (PDR; Laos), a landlocked country in Southeast Asia, has made important progress in reducing malaria morbidity and mortality in the past 5–6 years, and the northern provinces have very low reported incidence. To support national progress towards elimination, it is critical to verify and understand these changes in disease burden.

Methods
A two-stage cluster cross-sectional survey was conducted in four districts within four northern provinces (Khua, Phongsaly Province; Paktha, Bokeo Province; Nambak, Luang Prabang, and Muang Et, Huaphanh Province). During September and October 2016, demographics and malaria risk factors were collected from a total of 1492 …


Eliminate Now: Seven Critical Actions Required To Accelerate Elimination Of Plasmodium Falciparum Malaria In The Greater Mekong Subregion, Andrew A. Lover, Roly Gosling, Richard Feachem, Jim Tulloch Dec 2015

Eliminate Now: Seven Critical Actions Required To Accelerate Elimination Of Plasmodium Falciparum Malaria In The Greater Mekong Subregion, Andrew A. Lover, Roly Gosling, Richard Feachem, Jim Tulloch

Andrew Lover

The emergence in 2009 of Plasmodium falciparum parasites resistant to the primary therapies currently in use (artemisinin-based combination therapy, ACT) in Southeast Asia threatens to set back decades of global progress in malaria control and elimination. Progress to date through multiple sets of initiatives and partners to contain or eliminate these parasites has been hampered due to a wide range of organizational, financial, and health systems-level challenges. In this commentary, a set of seven specific and concrete actions are proposed to directly address these issues and to accelerate P. falciparum elimination within the Greater Mekong Subregion to avert a wider …


Hemocyte Differentiation Mediates The Mosquito Late-Phase Immune Response Against Plasmodium In Anopheles Gambiae, Ryan C. Smith, Carolina Barillas-Mury, Marcelo Jacobs-Lorena Jun 2015

Hemocyte Differentiation Mediates The Mosquito Late-Phase Immune Response Against Plasmodium In Anopheles Gambiae, Ryan C. Smith, Carolina Barillas-Mury, Marcelo Jacobs-Lorena

Ryan C. Smith

Plasmodium parasites must complete development in the mosquito vector for transmission to occur. The mosquito innate immune response is remarkably efficient in limiting parasite numbers. Previous work has identified a LPS-induced TNFα transcription factor (LITAF)-like transcription factor, LITAF-like 3 (LL3), which significantly influences parasite numbers. Here, we demonstrate that LL3 does not influence invasion of the mosquito midgut epithelium or ookinete-to-oocyst differentiation but mediates a late-phase immune response that decreases oocyst survival. LL3 expression in the midgut and hemocytes is activated by ookinete midgut invasion and is independent of the mosquito microbiota, suggesting that LL3 may be a component of …


Do Mixed Infections Matter? Assessing Virulence Of Mixed-Clone Infections In Experimental Human And Murine Malaria, Andrew A. Lover, Richard Coker Dec 2014

Do Mixed Infections Matter? Assessing Virulence Of Mixed-Clone Infections In Experimental Human And Murine Malaria, Andrew A. Lover, Richard Coker

Andrew Lover

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Background: Malaria parasites within an individual infection often consist of multiple strains (clonal populations) of a single species, which have the potential to interact both with one another, and with the host immune system. Several effects of these interactions have been measured in different parasite systems including competition and mutualism; however, direct observation of these effects in human malaria has been limited by sampling complexities and inherent ethical limitations.
Methods: Using multiple complementary epidemiological models, we propose a suite of analyses to more fully utilize …


Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald Dec 2014

Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald

Katherine A. Fitzgerald

Hemozoin (Hz) is the crystalline detoxification product of hemoglobin in Plasmodium-infected erythrocytes. We previously proposed that Hz can carry plasmodial DNA into a subcellular compartment that is accessible to Toll-like receptor 9 (TLR9), inducing an inflammatory signal. Hz also activates the NLRP3 inflammasome in primed cells. We found that Hz appears to colocalize with DNA in infected erythrocytes, even before RBC rupture or phagolysosomal digestion. Using synthetic Hz coated in vitro with plasmodial genomic DNA (gDNA) or CpG oligodeoxynucleotides, we observed that DNA-complexed Hz induced TLR9 translocation, providing a priming and an activation signal for inflammasomes. After phagocytosis, Hz and …


The Plasmodium Bottleneck: Malaria Parasite Losses In The Mosquito Vector, Ryan C. Smith, Joel Vega-Rodríguez, Marcelo Jacobs-Lorena Aug 2014

The Plasmodium Bottleneck: Malaria Parasite Losses In The Mosquito Vector, Ryan C. Smith, Joel Vega-Rodríguez, Marcelo Jacobs-Lorena

Ryan C. Smith

Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission.


Immunization Against A Merozoite Sheddase Promotes Multiple Invasion Of Red Blood Cells And Attenuates Plasmodium Infection In Mice, Ryan C. Smith, Daisy D. Colón-López, Jürgen Bosch Aug 2014

Immunization Against A Merozoite Sheddase Promotes Multiple Invasion Of Red Blood Cells And Attenuates Plasmodium Infection In Mice, Ryan C. Smith, Daisy D. Colón-López, Jürgen Bosch

Ryan C. Smith

Subtilisin-like protease 2 (SUB2) is a conserved serine protease utilized by Plasmodium parasites as a surface sheddase required for successful merozoite invasion of host red blood cells and has been implicated in ookinete invasion of the mosquito midgut. To determine if SUB2 is a suitable vaccine target to interfere with malaria parasite development, the effects of SUB2-immunization on the Plasmodium life cycle were examined in its vertebrate and invertebrate hosts. Swiss Webster mice were immunized with SUB2 peptides conjugated to Keyhole limpet hemocyanin (KLH) or KLH alone, and then challenged with Plasmodium berghei. To determine the effects of immunization on …


The Genome Of Anopheles Darlingi, The Main Neotropical Malaria Vector, Osvaldo Marinotti, Adam R. Wespiser, Daniel R. Caffrey, Douglas T. Golenbock, Neal S. Silverman Apr 2014

The Genome Of Anopheles Darlingi, The Main Neotropical Malaria Vector, Osvaldo Marinotti, Adam R. Wespiser, Daniel R. Caffrey, Douglas T. Golenbock, Neal S. Silverman

Neal Silverman

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors approximately 100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In …


Malaria-Related Knowledge And Prevention Practices In Four Neighbourhoods In And Around Mumbai, India: A Cross-Sectional Study, Gaurav Dhawan, Nidhin Joseph, Penelope S. Pekow, Christine A. Rogers, Krishna C. Poudel, Maria T. Bulzacchelli Jan 2014

Malaria-Related Knowledge And Prevention Practices In Four Neighbourhoods In And Around Mumbai, India: A Cross-Sectional Study, Gaurav Dhawan, Nidhin Joseph, Penelope S. Pekow, Christine A. Rogers, Krishna C. Poudel, Maria T. Bulzacchelli

Krishna C. Poudel

Background: India accounts for the highest number of malaria cases outside of Africa. Eighty per cent of India’s population lives in malaria-risk areas, with cases increasing in urban areas. Mumbai, India, one of the most populous cities in the world, has experienced such an increase. To be successful, many malaria control efforts require community participation, which in turn depends on individuals’ knowledge and awareness of the disease. This study assessed the knowledge and prevention practices regarding malaria in residents of four different areas of Mumbai, India, around the time of a malaria outbreak and the start of a widespread awareness …


Re-Assessing The Relationship Between Sporozoite Dose And Incubation Period In Plasmodium Vivax Malaria: A Systematic Re-Analysis, Andrew A. Lover, Richard Coker Dec 2013

Re-Assessing The Relationship Between Sporozoite Dose And Incubation Period In Plasmodium Vivax Malaria: A Systematic Re-Analysis, Andrew A. Lover, Richard Coker

Andrew Lover

Infections with the malaria parasite Plasmodium vivax are noteworthy for potentially very long incubation periods (6–9 months), which present a major barrier to disease elimination. Increased sporozoite challenge has been reported to be associated with both shorter incubation and pre-patent periods in a range of human challenge studies. However, this evidence base has scant empirical foundation, as these historical analyses were limited by available analytic methods, and provides no quantitative estimates of effect size. Following a comprehensive literature search, we re-analysed all identified studies using survival and/or logistic models plus contingency tables. We have found very weak evidence for dose- …


Regulation Of Anti-Plasmodium Immunity By A Litaf-Like Transcription Factor In The Malaria Vector Anopheles Gambiae, Ryan C. Smith, Abraham G. Eappen, Andrea J. Radtke, Marcelo Jacobs-Lorena Oct 2012

Regulation Of Anti-Plasmodium Immunity By A Litaf-Like Transcription Factor In The Malaria Vector Anopheles Gambiae, Ryan C. Smith, Abraham G. Eappen, Andrea J. Radtke, Marcelo Jacobs-Lorena

Ryan C. Smith

The mosquito is the obligate vector for malaria transmission. To complete its development within the mosquito, the malaria parasite Plasmodium must overcome the protective action of the mosquito innate immune system. Here we report on the involvement of the Anopheles gambiae orthologue of a conserved component of the vertebrate immune system, LPS-induced TNFα transcription factor (LITAF), and its role in mosquito anti-Plasmodium immunity. An. gambiae LITAF-like 3 (LL3) expression is up-regulated in response to midgut invasion by both rodent and human malaria parasites. Silencing of LL3 expression greatly increases parasite survival, indicating that LL3 is part of an anti-Plasmodium defense …


The Impact Of Anaemia And Malaria Parasite Infection In Pregnant Women, Nigerian Perspective., Ifeyinwa M. Okafor Dr., M Mbah, E A. Usanga Jul 2012

The Impact Of Anaemia And Malaria Parasite Infection In Pregnant Women, Nigerian Perspective., Ifeyinwa M. Okafor Dr., M Mbah, E A. Usanga

Okafor Ifeyinwa M Dr.

Malaria and anaemia during pregnancy is still a major health problem in endemic countries with clinical consequences including death of both mother and child. In Nigeria, statistics shows that as many as 300,000 lives especially those of children and pregnant women are lost annually due to malaria. This study was aimed at assessing the impact of malaria and anaemia among pregnant women living in Calabar South Local Government Area of Cross River State, Nigeria, which is characterized by unstable transmission of malaria. .A total of 664 subjects were enrolled in the study made up of 414 pregnant women attending antenatal …


Use Of Herbal Medicine In The Management Of Malaria In The Urban-Periphery, Ghana, Charlotte Monica Mensah, Razak Mohammed Gyasi Dec 2011

Use Of Herbal Medicine In The Management Of Malaria In The Urban-Periphery, Ghana, Charlotte Monica Mensah, Razak Mohammed Gyasi

Mr. GYASI Razak Mohammed

Herbal medicine use has been reported a common practice among individuals with clinical and complicated malaria but correlates of herbal medicine use among malaria subjects remain implicit. This cross-sectional study analysed the frequency of and factors associated with utilization of herbal medical services amongst malaria victims in urban-periphery, Kwabre East District, Ghana. A total of 189 malaria subjects and 5 traditional medical providers were respectively selected through systematic random sampling and snowball technique for the study. Structured and in-depth interview guides were utilised as the main data collection instruments. Whilst the quantitative data were analyzed using linear regression model through …


An Exploratory Study Of Treated-Bed Nets In Timor-Leste: Patterns Of Intended And Alternative Usage, Andrew A. Lover, Brett A. Sutton, Angelina J. Asy, Annelies Wilder-Smith Dec 2010

An Exploratory Study Of Treated-Bed Nets In Timor-Leste: Patterns Of Intended And Alternative Usage, Andrew A. Lover, Brett A. Sutton, Angelina J. Asy, Annelies Wilder-Smith

Andrew Lover

Background
The Timor-Leste Ministry of Health has recently finalized the National Malaria Control Strategy for 2010-2020. A key component of this roadmap is to provide universal national coverage with long-lasting insecticide-treated nets (LLINs) in support of achieving the primary goal of reducing both morbidity and mortality from malaria by 30% in the first three years, followed by a further reduction of 20% by end of the programme cycle in 2020 [1]. The strategic plan calls for this target to be supported by a comprehensive information, education and communication (IEC) programme; however, there is limited prior research into household …


Anopheles Gambiae Purine Nucleoside Phosphorylase: Catalysis, Structure And Inhibition, Erika Taylor, Agnes Rinaldo-Matthis, Lei Li, Mahmoud Ghanem, Keith Hazleton, M. Belen Cassera, Steven Almo, Vern Schramm Oct 2007

Anopheles Gambiae Purine Nucleoside Phosphorylase: Catalysis, Structure And Inhibition, Erika Taylor, Agnes Rinaldo-Matthis, Lei Li, Mahmoud Ghanem, Keith Hazleton, M. Belen Cassera, Steven Almo, Vern Schramm

Erika A. Taylor, Ph.D.

The purine salvage pathway of Anopheles gambiae, a mosquito that transmits malaria, has been identified in genome searches on the basis of sequence homology with characterized enzymes. Purine nucleoside phosphorylase (PNP) is a target for the development of therapeutic agents in humans and purine auxotrophs, including malarial parasites. The PNP from Anopheles gambiae (AgPNP) was expressed in Escherichia coli and compared to the PNPs from Homo sapiens (HsPNP) and Plasmodium falciparum (PfPNP). AgPNP has kcat values of 54 and 41 s-1 for 2'-deoxyinosine and inosine, its preferred substrates, and 1.0 s-1 for guanosine. However, the chemical step is fast for …


Sds-Page And Western Blotting Of Plasmodium Falciparum Proteins, Roland A. Cooper Jun 2002

Sds-Page And Western Blotting Of Plasmodium Falciparum Proteins, Roland A. Cooper

Roland A. Cooper

The Plasmodium spp. parasite was identified as the causative agent of malaria in 1880, and the mosquito was identified as the vector in 1897. Despite subsequent efforts focused on the epidemiology, cell biology, immunology, molecular biology, and clinical manifestations of malaria and the Plasmodium parasite, there is still no licensed vaccine for the prevention of malaria. Physical barriers (bed nets, window screens) and chemical prevention methods (insecticides and mosquito repellents) intended to interfere with the transmission of the disease are not highly effective, and the profile of resistance of the parasite to chemoprophylactic and chemotherapeutic agents is increasing. The dawn …


Allelic Modifications Of The Cg2 And Cg1 Genes Do Not Alter The Chloroquine Response Of Drug-Resistant Plasmodium Falciparum, David A. Fidock, Takashi Nomura, Roland A. Cooper, Xin-Zhuan Su, Angela K. Talley, Thomas E. Wellems Aug 2000

Allelic Modifications Of The Cg2 And Cg1 Genes Do Not Alter The Chloroquine Response Of Drug-Resistant Plasmodium Falciparum, David A. Fidock, Takashi Nomura, Roland A. Cooper, Xin-Zhuan Su, Angela K. Talley, Thomas E. Wellems

Roland A. Cooper

The determinant of chloroquine resistance (CQR) in a Plasmodium falciparum cross was previously mapped by linkage analysis to a 36 kb segment of chromosome 7. Candidate genes within this segment have been previously shown to include two genes, cg2 and cg1, that have complex polymorphisms linked to the CQR phenotype. Using DNA transfection and allelic exchange, we have replaced these polymorphisms in CQR parasites with cg2 and cg1 sequences from chloroquine sensitive parasites. Drug assays of the allelically-modified lines show no change in the degree of CQR, providing evidence against the hypothesis that these polymorphisms are important to the CQR …