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Malaria medicines: a glass half full?

CiteULike malaria tags - 9 February 2016 - 12:38am
Nat Rev Drug Discov, Vol. 14, No. 6. (22 June 2015), pp. 424-442, doi:10.1038/nrd4573

Despite substantial scientific progress over the past two decades, malaria remains a worldwide burden that causes hundreds of thousands of deaths every year. New, affordable and safe drugs are required to overcome increasing resistance against artemisinin-based treatments, treat vulnerable populations, interrupt the parasite life cycle
Timothy Wells, Rob van Huijsduijnen, Wesley Van Voorhis
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Unusual antibodies target malaria

CiteULike malaria tags - 7 February 2016 - 7:48pm
Science, Vol. 351, No. 6273. (04 February 2016), pp. 572-573, doi:10.1126/science.351.6273.572-f
KL Mueller
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Comparative genome-wide analysis and evolutionary history of haemoglobin-processing and haem detoxification enzymes in malarial parasites

CiteULike malaria tags - 4 February 2016 - 12:54pm
Malaria Journal, Vol. 15, No. 1. (29 January 2016), doi:10.1186/s12936-016-1097-9
Patrath Ponsuwanna, Theerarat Kochakarn, Duangkamon Bunditvorapoom, Krittikorn Kümpornsin, Thomas Otto, Chase Ridenour, Kesinee Chotivanich, Prapon Wilairat, Nicholas White, Olivo Miotto, Thanat Chookajorn
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Association of anemia, pre-eclampsia and eclampsia with seasonality: A realist systematic review

CiteULike malaria tags - 31 January 2016 - 4:23pm
Health & Place, Vol. 31 (January 2015), pp. 180-192, doi:10.1016/j.healthplace.2014.12.003
Tina Hlimi
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Beyond DNA binding - a review of the potential mechanisms mediating quinacrine's therapeutic activities in parasitic infections, inflammation, and cancers.

CiteULike malaria tags - 28 January 2016 - 9:16pm
Cell communication and signaling : CCS, Vol. 9 (15 May 2011), 13, doi:10.1186/1478-811x-9-13

This is an in-depth review of the history of quinacrine as well as its pharmacokinetic properties and established record of safety as an FDA-approved drug. The potential uses of quinacrine as an anti-cancer agent are discussed with particular attention to its actions on nuclear proteins, the arachidonic acid pathway, and multi-drug resistance, as well as its actions on signaling proteins in the cytoplasm. In particular, quinacrine's role on the NF-κB, p53, and AKT pathways are summarized.
Reza Ehsanian, Carter Van Waes, Stephan Feller
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Epidemiology and Clinical Burden of Malaria in the War-Torn Area, Orakzai Agency in Pakistan

CiteULike malaria tags - 26 January 2016 - 6:20am
PLoS Negl Trop Dis, Vol. 10, No. 1. (25 January 2016), e0004399, doi:10.1371/journal.pntd.0004399

Military conflict has been a major challenge in the detection and control of emerging infectious diseases such as malaria. It poses issues associated with enhancing emergence and transmission of infectious diseases by destroying infrastructure and collapsing healthcare systems. The Orakzai agency in Pakistan has witnessed a series of intense violence and destruction. Military conflicts and instability in Afghanistan have resulted in the migration of refugees into the area and possible introduction of many infectious disease epidemics. Due to the ongoing violence and Talibanization, it has been a challenge to conduct an epidemiological study. All patients were sampled within the transmission season. After a detailed clinical investigation of patients, data were recorded. Baseline venous blood samples were taken for microscopy and nested polymerase chain reaction (nPCR) analysis. Plasmodium species were detected using nested PCR (nPCR) and amplification of the small subunit ribosomal ribonucleic acid (ssrRNA) genes using the primer pairs. We report a clinical assessment of the epidemic situation of malaria caused by Plasmodium vivax (86.5%) and Plasmodium falciparum (11.79%) infections with analysis of complications in patients such as decompensated shock (41%), anemia (8.98%), hypoglycaemia (7.3%), multiple convulsions (6.7%), hyperpyrexia (6.17%), jaundice (5%), and hyperparasitaemia (4.49%). This overlooked distribution of P. vivax should be considered by malaria control strategy makers in the world and by the Government of Pakistan. In our study, children were the most susceptible population to malaria infection while they were the least expected to use satisfactory prevention strategies in such a war-torn deprived region. Local health authorities should initiate malaria awareness programs in schools and malaria-related education should be further promoted at the local level reaching out to both children and parents. The malaria epidemic and endemic in Pakistan is a present and ongoing threat to public health which could have an impact in the nearby regions as well. For the first time, we report a clinical assessment of malaria endemicity in the Orakzai Agency, which is Pakistan’s most neglected area due to Talibanization and war in Afghanistan. Febrile patient blood samples of the area were investigated to report the clinical assessment of malaria caused by Plasmodium vivax and P. falciparum infections. The nested polymerase chain reaction (nPCR) examination detected 154 (86%) and 21 (12%) P. vivax and P. falciparum infections, respectively. We found worsening hygiene conditions in FATA, likely caused by poor socioeconomics and the collapse of the public health infrastructure. Decompensated shock was a common and prominent clinical feature of malaria among all the clinical presentations caused by both P. vivax (53%) and P. falciparum (42.9%). Our results have significant implications for both public health and malaria control in FATA and Pakistan. Our findings illustrate higher prevalence of malaria in children compared to other age groups. Further research on sensible estimates of refugees is required, as well as resistance to anti-malarials.
Asad Karim, Irfan Hussain, Sumera Malik, Jung Lee, Ill Cho, Young Kim, Sang Lee
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Efficient Correction of the Sickle Mutation in Human Hematopoietic Stem Cells Using a Cas9 Ribonucleoprotein Complex

CiteULike malaria tags - 24 January 2016 - 6:13pm
bioRxiv (15 January 2016), 036236, doi:10.1101/036236

bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
Mark DeWitt, Wendy Magis, Nicolas Bray, Tianjiao Wang, Jennifer Berman, Fabrizia Urbinati, Denise Muñoz, Donald Kohn, Mark Walters, Dana Carroll, David Martin, Jacob Corn
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Dihydroartemisinin–piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study

CiteULike malaria tags - 21 January 2016 - 9:56am
The Lancet Infectious Diseases (January 2016), doi:10.1016/s1473-3099(15)00487-9
Chanaki Amaratunga, Pharath Lim, Seila Suon, Sokunthea Sreng, Sivanna Mao, Chantha Sopha, Baramey Sam, Dalin Dek, Vorleak Try, Roberto Amato, Daniel Blessborn, Lijiang Song, Gregory Tullo, Michael Fay, Jennifer Anderson, Joel Tarning, Rick Fairhurst
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Localization and interactions of <it>Plasmodium falciparum</it> SWIB/MDM2 homologues

Malaria Journal - 20 January 2016 - 12:00pm
Background: Malaria remains a global health problem and the majority of deaths are caused by Plasmodium falciparum parasites. Due to the rapid emergence of drug-resistant strains, novel avenues of research on the biology of the parasite are needed. The massive proliferation of asexual, intra-erythrocytic parasites every 48 h could kill the human host prior to transmission of slow-developing gametocytes to the mosquito vector. A self-induced P. falciparum programmed cell death mechanism has been hypothesized to maintain this balance between the parasite and its two hosts, but molecular participants of the cell death pathway in P. falciparum have not been characterized. Proteins with SWIB/MDM2 domains play a key role in metazoan programmed cell death and this study provides the first evaluation of two parasite SWIB/MDM2 homologues, PF3D7_0518200 (PfMDM2) and PF3D7_0611400 (PfSWIB). Methods: The function of these proteins was assessed by predicting their structural topology with the aid of bioinformatics and determining their location within live transgenic parasites, expressing green fluorescent protein-tagged PfMDM2 and PfSWIB under normal and elevated temperatures, which mimic fever and which are known to induce a programmed cell death response. Additionally, P. falciparum phage display library technology was used to identify binding partners for the two parasite SWIB/MDM2 domains. Results: Structural features of the SWIB/MDM2 domains of PfMDM2 and PfSWIB, suggested that they are chromatin remodelling factors. The N-terminal signal sequence of PfMDM2 directed the protein to the mitochondrion under both normal and heat stress conditions. Plasmodium falciparum phage display library technology revealed that the C-terminal SWIB/MDM2 domain of PfMDM2 interacted with a conserved protein containing a LisH domain. PfSWIB localized to the cytoplasm under normal growth conditions, while approximately 10 % of the heat-stressed trophozoite-stage parasites presented a rapid but short-lived nuclear localization pattern. Two PfSWIB binding partners, a putative Aurora-related kinase and a member of the inner membrane complex, were identified. Conclusion: These novel data provide insight into the function of two parasite SWIB/MDM2 homologues and suggest that PfMDM2 plays a role within the mitochondrion and that PfSWIB is involved in a stage-specific, heat-stress, response pathway.
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Field evaluation of the 22 rapid diagnostic tests for community management of malaria with artemisinin combination therapy in Cameroon

Malaria Journal - 20 January 2016 - 12:00pm
Background: All suspected cases of malaria should receive a diagnostic test prior to treatment with artemisinin-based combinations based on the new WHO malaria treatment guidelines. This study compared the accuracy and some operational characteristics of 22 different immunochromatographic antigen capture point-of- malaria tests (RDTs) in Cameroon to inform test procurement prior to deployment of artemisinin-based combinations for malaria treatment. Methods: One hundred human blood samples (50 positive and 50 negative) collected from consenting febrile patients in two health centres at Yaoundé were used for evaluation of the 22 RDTs categorized as “Pf Only” (9) or “Pf + PAN” (13) based on parasite antigen captured [histidine rich protein II (HRP2) or lactate dehydrogenase (pLDH) or aldolase]. RDTs were coded to blind technicians performing the tests. The sensitivity, specificity, and predictive values of the positive and negative tests (PPV and NPV) as well as the likelihood ratios were assessed. The reliability and some operational characteristics were determined as the mean values from two assessors, and the Cohen’s kappa statistic was then used to compare agreement. Light microscopy was the referent. Results: Of all RDTs tested, 94.2 % (21/22) had sensitivity values greater than 90 % among which 14 (63.6 %) were ‘Pf + PAN’ RDTs. The specificity was generally lower than the sensitivity for all RDTs and poorer for “Pf Only” RDTs. The predictive values and likelihood ratios were better for non-HRP2 analytes for “Pf + PAN” RDTs. The Kappa value for most of the tests obtained was around 67 % (95 % CI 50–69 %), corresponding to a moderate agreement. Conclusion: Overall, 94.2 % (21/22) of RDTs tested had accuracy within the range recommended by the WHO, while one performed poorly, below acceptable levels. Seven “Pf + PAN” and 3 “Pf Only” RDTs were selected for further assessment based on performance characteristics. Harmonizing RDT test presentation and procedures would prevent mistakes of test performance and interpretation.
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UTR introns, antisense RNA and differentially spliced transcripts between <it>Plasmodium yoelii</it> subspecies

Malaria Journal - 20 January 2016 - 12:00pm
Background: The rodent malaria parasite Plasmodium yoelii is an important animal model for studying host-parasite interaction and molecular basis of malaria pathogenesis. Although a draft genome of P. yoelii yoelii YM is available, and RNA sequencing (RNA-seq) data for several rodent malaria species (RMP) were reported recently, variations in coding regions and structure of mRNA transcript are likely present between different parasite strains or subspecies. Sequencing of cDNA libraries from additional parasite strains/subspecies will help improve the gene models and genome annotation. Methods: Here two directional cDNA libraries from mixed blood stages of a subspecies of P. yoelii (P. y. nigeriensis NSM) with or without mefloquine (MQ) treatment were sequenced, and the sequence reads were compared to the genome and cDNA sequences of P. y. yoelii YM in public databases to investigate single nucleotide polymorphisms (SNPs) in coding regions, variations in intron–exon structure and differential splicing between P. yoelii subspecies, and variations in gene expression under MQ pressure. Results: Approximately 56 million of 100 bp paired-end reads were obtained, providing an average of ~225-fold coverage for the coding regions. Comparison of the sequence reads to the YM genome revealed introns in 5′ and 3′ untranslated regions (UTRs), altered intron/exon boundaries, alternative splicing, overlapping sense-antisense reads, and potentially new transcripts. Interestingly, comparison of the NSM RNA-seq reads obtained here with those of YM discovered differentially spliced introns; e.g., spliced introns in one subspecies but not the other. Alignment of the NSM cDNA sequences to the YM genome sequence also identified ~84,000 SNPs between the two parasites. Conclusion: The discoveries of UTR introns and differentially spliced introns between P. yoelii subspecies raise interesting questions on the potential role of these introns in regulating gene expression and evolution of malaria parasites.
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Distribution of Fc&#947;R gene polymorphisms among two sympatric populations in Mali: differing allele frequencies, associations with malariometric indices and implications for genetic susceptibility to malaria

Malaria Journal - 19 January 2016 - 12:00am
Background: Genetic polymorphisms in the complex gene cluster encoding human Fc-gamma receptors (FcγRs) may influence malaria susceptibility and pathogenesis. Studying genetic susceptibility to malaria is ideal among sympatric populations because the distribution of polymorphic genes among such populations can help in the identification malaria candidate genes. This study determined the distribution of three FcyRs single nucleotide polymorphisms (SNPs) (FcγRIIB-rs1050519, FcγRIIC-rs3933769 and FcγRIIIA-rs396991) among sympatric Fulani and Dogon children with uncomplicated malaria. The association of these SNPs with clinical, malariometric and immunological indices was also tested. Methods: This study involved 242 Fulani and Dogon volunteers from Mali age under 15 years. All SNPs were genotyped with predesigned TaqMan ® SNP Genotyping Assays. Genotypic and allelic distribution of SNPs was compared across ethnic groups using the Fisher exact test. Variations in clinical, malariometric and immunologic indices between groups were tested with Kruskal–Wallis H, Mann–Whitney U test and Fisher exact test where appropriate. Results: The study confirmed known malariometric and immunologic differences between sympatric Fulani and non-Fulani tribes. Parasite density was lower in the Fulani than the Dogon (p < 0.0001). The mutant allele of FcγRIIC (rs3933769) was found more frequently in the Fulani than the Dogon (p < 0.0001) while that of FcγRIIIA (rs396991) occurred less frequently in the Fulani than Dogon (p = 0.0043). The difference in the mutant allele frequency of FcγRIIB (rs1050519) between the two ethnic groups was however not statistically significant (p = 0.064). The mutant allele of rs396991 was associated with high malaria-specific IgG1 and IgG3 in the entire study population and Dogon tribe, p = 0.023 and 0.015, respectively. Parasite burden was lower in carriers of the FcγRIIC (rs3933769) mutant allele than non-carriers in the entire study population (p < 0.0001). Carriers of this allele harboured less than half the parasites found in non-carriers. Conclusion: Differences in the allelic frequencies of rs3933769 and rs396991 among Fulani and Dogon indirectly suggest that these SNPs may influence malaria susceptibility and pathogenesis in the study population. The high frequency of the FcγRIIC (rs3933769) mutant allele in the Fulani and its subsequent association with low parasite burden in the entire study population is noteworthy.
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Functional analysis of monoclonal antibodies against the <it>Plasmodium falciparum</it> PfEMP1-VarO adhesin

Malaria Journal - 15 January 2016 - 12:00pm
Background: Rosetting, namely the capacity of the Plasmodium falciparum-infected red blood cells to bind uninfected RBCs, is commonly observed in African children with severe malaria. Rosetting results from specific interactions between a subset of variant P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesins encoded by var genes, serum components and RBC receptors. Rosette formation is a redundant phenotype, as there exists more than one var gene encoding a rosette-mediating PfEMP1 in each genome and hence a diverse array of underlying interactions. Moreover, field diversity creates a large panel of rosetting-associated serotypes and studies with human immune sera indicate that surface-reacting antibodies are essentially variant-specific. To gain better insight into the interactions involved in rosetting and map surface epitopes, a panel of monoclonal antibodies (mAbs) was investigated. Methods: Monoclonal antibodies were isolated from mice immunized with PfEMP1-VarO recombinant domains. They were characterized using ELISA and reactivity with the native PfEMP1-VarO adhesin on immunoblots of reduced and unreduced extracts, as well as SDS-extracts of Palo Alto 89F5 VarO schizonts. Functionality was assessed using inhibition of Palo Alto 89F5 VarO rosette formation and disruption of Palo Alto 89F5 VarO rosettes. Competition ELISAs were performed with biotinylated antibodies against DBL1 to identify reactivity groups. Specificity of mAbs reacting with the DBL1 adhesion domain was explored using recombinant proteins carrying mutations abolishing RBC binding or binding to heparin, a potent inhibitor of rosette formation. Results: Domain-specific, surface-reacting mAbs were obtained for four individual domains (DBL1, CIDR1, DBL2, DBL4). Monoclonal antibodies reacting with DBL1 potently inhibited the formation of rosettes and disrupted Palo Alto 89F5 VarO rosettes. Most surface-reactive mAbs and all mAbs interfering with rosetting reacted on parasite immunoblots with disulfide bond-dependent PfEMP1 epitopes. Based on competition ELISA and binding to mutant DBL1 domains, two distinct binding sites for rosette-disrupting mAbs were identified in close proximity to the RBC-binding site. Conclusions: Rosette-inhibitory antibodies bind to conformation-dependent epitopes located close to the RBC-binding site and distant from the heparin-binding site. These results provide novel clues for a rational intervention strategy that targets rosetting.
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Heterogeneous alleles comprising G6PD deficiency trait in West Africa exert contrasting effects on two major clinical presentations of severe malaria

CiteULike malaria tags - 14 January 2016 - 1:40pm
Malaria Journal, Vol. 15, No. 1. (07 January 2016), 13, doi:10.1186/s12936-015-1045-0

Glucose-6-phosphate dehydrogenase (G6PD) deficiency exhibits considerable allelic heterogeneity which manifests with variable biochemical and clinical penetrance. It has long been thought that G6PD deficiency confers partial protection against severe malaria, however prior genetic association studies have disagreed with regard to the strength and specificity of a protective effect, which might reflect differences in the host genetic background, environmental influences, or in the specific clinical phenotypes considered.
Shivang Shah, Kirk Rockett, Muminatou Jallow, Fatou Sisay-Joof, Kalifa Bojang, Margaret Pinder, Anna Jeffreys, Rachel Craik, Christina Hubbart, Thomas Wellems, Dominic Kwiatkowski, $Author
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Environmental correlation analysis for genes associated with protection against malaria

CiteULike malaria tags - 14 January 2016 - 1:26pm
Molecular Biology and Evolution (06 January 2016), msw004, doi:10.1093/molbev/msw004

Genome-wide searches for loci involved in human resistance to malaria are currently being conducted on a large scale in Africa using case-control studies. Here, we explore the utility of an alternative approach – “environmental correlation analysis, ECA”, which tests for clines in allele frequencies across a gradient of an environmental selection pressure - to identify genes that have historically protected against death from malaria. We collected genotype data from 12,425 newborns on 57 candidate malaria resistance loci and 9,756 SNPs selected at random from across the genome, and examined their allele frequencies for geographic correlations with long-term malaria prevalence data based on 84,042 individuals living under different historical selection pressures from malaria in coastal Kenya. None of the 57 candidate SNPs showed significant (P < 0.05) correlations in allele frequency with local malaria transmission intensity after adjusting for population structure and multiple testing. By contrast, two of the random SNPs that had highly significant correlations (P < 0.01) were in genes previously linked to malaria resistance, namely, CDH13, encoding cadherin 13, and HS3ST3B1, encoding heparan sulphate 3-O-sulfotransferase 3B1. Both proteins play a role in glycoprotein-mediated cell-cell adhesion which has been widely implicated in cerebral malaria, the most life-threatening form of this disease. Other top genes, including CTNND2 which encodes δ-catenin, a molecular partner to cadherin, were significantly enriched in cadherin-mediated pathways affecting inflammation of the brain vascular endothelium. These results demonstrate the utility of ECA in the discovery of novel genes and pathways affecting infectious disease.
Margaret Mackinnon, Carolyne Ndila, Sophie Uyoga, Alex Macharia, Robert Snow, Gavin Band, Anna Rautanen, Kirk Rockett, Dominic Kwiatkowski, Thomas Williams, in collaboration with the MalariaGEN Consortium
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Identification, Validation, and Application of Molecular Diagnostics for Insecticide Resistance in Malaria Vectors

CiteULike malaria tags - 14 January 2016 - 11:52am
Trends in Parasitology (December 2015), doi:10.1016/j.pt.2015.12.001

Insecticide resistance is a major obstacle to control of Anopheles malaria mosquitoes in sub-Saharan Africa and requires an improved understanding of the underlying mechanisms. Efforts to discover resistance genes and DNA markers have been dominated by candidate gene and quantitative trait locus studies of laboratory strains, but with greater availability of genome sequences a shift toward field-based agnostic discovery is anticipated. Mechanisms evolve continually to produce elevated resistance yielding multiplicative diagnostic markers, co-screening of which can give high predictive value. With a shift toward prospective analyses, identification and screening of resistance marker panels will boost monitoring and programmatic decision making. Insecticide resistance in African Anopheles malaria vectors is a growing problem. Diagnosis and monitoring for insecticide resistance management would be aided by wider application of DNA markers. Protein-altering mutations in the conserved genes encoding insecticide target sites are often associated with insecticide resistance and are readily diagnosed. Emerging studies suggest that mutations accumulate in these genes and can act synergistically. Convergent results identify cytochrome P450s as crucial in metabolic resistance. Some of these genes confer resistance across multiple insecticides but few DNA markers are available. New genomic resources and functional validation approaches will shortly yield additional resistance-associated variants for monitoring and evaluation.
Martin Donnelly, Alison Isaacs, David Weetman
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Calcium signalling in malaria parasites

CiteULike malaria tags - 14 January 2016 - 11:03am
Molecular Microbiology (1 January 2016), pp. n/a-n/a, doi:10.1111/mmi.13324

Ca2+ is a ubiquitous intracellular messenger in malaria parasites with important functions in asexual blood stages responsible for malaria symptoms, the preceding liver-stage infection and transmission through the mosquito. Intracellular messengers amplify signals by binding to effector molecules that trigger physiological changes. The characterisation of some Ca2+ effector proteins has begun to provide insights into the vast range of biological processes controlled by Ca2+ signalling in malaria parasites, including host cell egress and invasion, protein secretion, motility, and cell cycle regulation. Despite the importance of Ca2+ signalling during the life cycle of malaria parasites, little is known about Ca2+ homeostasis. Recent findings highlighted that upstream of stage-specific Ca2+ effectors is a conserved interplay between second messengers to control critical intracellular Ca2+ signals throughout the life cycle. The identification of the molecular mechanisms integrating stagetranscending mechanisms of Ca2+ homeostasis in a network of stage-specific regulator and effector pathways now represents a major challenge for a meaningful understanding of Ca2+ signalling in malaria parasites. This article is protected by copyright. All rights reserved.
Mathieu Brochet, Oliver Billker
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A malaria risk map of Kinshasa, Democratic Republic of Congo

Malaria Journal - 13 January 2016 - 12:00pm
Background: In Kinshasa, malaria remains a major public health problem but its spatial epidemiology has not been assessed for decades now. The city’s growth and transformation, as well as recent control measures, call for an update. To identify highly exposed communities and areas where control measures are less critically needed, detailed risk maps are required to target control and optimize resource allocation. Methods: In 2009 (end of the dry season) and 2011 (end of the rainy season), two cross-sectional surveys were conducted in Kinshasa to determine malaria prevalence, anaemia, history of fever, bed net ownership and use among children 6–59 months. Geo-referenced data for key parameters were mapped at the level of the health area (HA) by means of a geographic information system (GIS). Results: Among 7517 children aged 6–59 months from 33 health zones (HZs), 6661 (3319 in 2009 and 3342 in 2011) were tested for both malaria (by Rapid Diagnostic Tests) and anaemia, and 856 (845 in 2009 and 11 in 2011) were tested for anaemia only. Fifteen HZs were sampled in 2009, 25 in 2011, with seven HZs sampled in both surveys. Mean prevalence for malaria and anaemia was 6.4 % (5.6–7.4) and 65.1 % (63.7–66.6) in 2009, and 17.0 % (15.7–18.3) and 64.2 % (62.6–65.9) in 2011. In two HZs sampled in both surveys, malaria prevalence was 14.1 % and 26.8 % in Selembao (peri-urban), in the 2009 dry season and 2011 rainy season respectively, and it was 1.0 % and 0.8 % in Ngiri Ngiri (urban). History of fever during the preceding two weeks was 13.2 % (12.5–14.3) and 22.3 % (20.8–23.4) in 2009 and 2011. Household ownership of at least one insecticide-treated net (ITN) was 78.7 % (77.4–80.0) and 65.0 % (63.7–66.3) at both time points, while use was 57.7 % (56.0–59.9) and 45.0 % (43.6–46.8), respectively. Conclusions: This study presents the first malaria risk map of Kinshasa, a mega city of roughly 10 million inhabitants and located in a highly endemic malaria zone. Prevalence of malaria, anaemia and reported fever was lower in urban areas, whereas low coverage of ITN and sub-optimal net use were frequent in peri-urban areas.
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Sickle haemoglobin, haemoglobin C and malaria mortality feedbacks

Malaria Journal - 12 January 2016 - 12:00am
Background: Sickle haemoglobin (HbS) and haemoglobin C (HbC) are both caused by point mutations in the beta globin gene, and both offer substantial malaria protection. Despite the fact that the blood disorder caused by homozygosity for HbC is much less severe than that caused by homozygosity for HbS (sickle cell anaemia), it is the sickle mutation which has come to dominate many old-world malarious regions, whilst HbC is highly restricted in its geographical distribution. It has been suggested that this discrepancy may be due to sickle cell heterozygotes enjoying a higher level of malaria protection than heterozygotes for HbC. A higher fitness of sickle cell heterozygotes relative to HbC heterozygotes could certainly have allowed the sickle cell allele to spread more rapidly. However, observations that carrying either HbC or HbS enhances an individual’s capacity to transmit malaria parasites to mosquitoes could also shed light on this conundrum. Methods: A population genetic model was used to investigate the evolutionary consequences of the strength of malaria selection being correlated with either HbS frequency or HbC frequency. Results: If the selection pressure from malaria is positively correlated with the frequency of either HbS or HbC, it is easier for HbS to succeed in the competitive interaction between the two alleles. Conclusions: A feedback process whereby the presence of variant haemoglobins increases the level of malaria selection in a population could have contributed to the global success of HbS relative to HbC, despite the former’s higher blood disorder cost.
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Malaria transmission dynamics surrounding the first nationwide long-lasting insecticidal net distribution in Papua New Guinea

Malaria Journal - 12 January 2016 - 12:00am
Background: The major malaria vectors of Papua New Guinea exhibit heterogeneities in distribution, biting behaviour and malaria infection levels. Long-lasting, insecticide-treated nets (LLINs), distributed as part of the National Malaria Control Programme, are the primary intervention targeting malaria transmission. This study evaluated the impact of LLINs on anopheline density, species composition, feeding behaviour, and malaria transmission. Methods: Mosquitoes were collected by human landing catch in 11 villages from East Sepik Province and Madang Province. Mosquitoes were collected for 3 years (1 year before distribution and 2 years after), and assayed to determine mosquito species and Plasmodium spp. infection prevalence. The influence of weather conditions and the presence of people and animals on biting density was determined. Determinants of biting density and sporozoite prevalence were analysed by generalized estimating equations (GEE). Results: Mosquito biting rates and entomological inoculation rates decreased significantly after the distribution. Plasmodium falciparum and P. vivax sporozoite prevalence decreased in year 2, but increased in year 3, suggesting the likelihood of resurgence in transmission if low biting rates are not maintained. An earlier shift in the median biting time of Anopheles punctulatus and An. farauti s.s. was observed. However, this was not accompanied by an increase in the proportion of infective bites occurring before 2200 hours. A change in species composition was observed, which resulted in dominance of An. punctulatus in Dreikikir region, but a decrease in An. punctulatus in the Madang region. When controlling for village and study year, An. farauti s.s., An. koliensis and An. punctulatus were equally likely to carry P. vivax sporozoites. However, An. punctulatus was significantly more likely than An. farauti s.s. (OR 0.14; p = 0.007) or An. koliensis (OR 0.27; p < 0.001) to carry P. falciparum sporozoites. Conclusions: LLINs had a significant impact on malaria transmission, despite exophagic and crepuscular feeding behaviours of dominant vectors. Changes in species composition and feeding behaviour were observed, but their epidemiological significance will depend on their durability over time.
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