By 2080, parts of Germany could be susceptible to the spread of malaria for up to six months a year, according to new research. The study mapped areas at risk of an outbreak, considering predicted climate change-driven rise in air temperature and data on the spread of malaria.

A recent study has projected changes in the spread of malaria caused by climate change and climate variability in Africa by including the effect of variations in land use on local climate. It concludes that the risk of malaria epidemics is likely to shift from the north to the south of the Sahel, and to highland areas previously free of the disease.

Biodiversity could play a key role in preventing future outbreaks of malaria in tropical forests, according to a new study. Results indicate that a greater number of mosquito species could increase competition for mosquitoes that spread malarial parasites, whilst more vertebrate species could increase the likelihood that malarial parasites end up in 'dead-end hosts' that are unable to transmit the disease any further.

Grandma's chicken soup has got nothing on these miraculous broths.

On World Mosquito Day, August 20, mission agency enlists public to help combat airborne killer

Kenyan scientists discovered a microbe–Microsporidia MB–inside some mosquitoes that completely protects them from malaria infection which spreads to humans.

The post Breakthrough For Kenyan Scientists Who Discover Natural Microbe That Completely Stops Malaria in Mosquitoes appeared first on Good News Network.

Treating patients with "moderate" COVID-19 is a way to stop the disease from progressing to a severe stage that would require mechanical ventilation.

Hydroxychloroquine, the drug President Trump hailed as a coronavirus killer, had no beneficial effect for COVID-19 patients in two controlled trials.

Scientists say the microbe - found in the wild near Lake Victoria - has enormous potential.

Here are the latest developments in the coronavirus crisis.

Researchers have engineered bacteria to produce new versions of a potential antibiotic molecule, some with potent antimalarial properties.

The increasing incidence of antimalarial drug resistance to the first-line artemisinin combination therapies underpins an urgent need for new antimalarial drugs, ideally with a novel mode of action. The recently developed 2-aminomethylphenol, JPC-3210, (MMV 892646) is an erythrocytic schizonticide with potent in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum lines, low cytotoxicity, potent in vivo efficacy against murine malaria, and favorable preclinical pharmacokinetics including a lengthy plasma elimination half-life. To investigate the impact of JPC-3210 on biochemical pathways within P. falciparum-infected red blood cells, we have applied a "multi-omics" workflow based on high resolution orbitrap mass spectrometry combined with biochemical approaches. Metabolomics, peptidomics and hemoglobin fractionation analyses revealed a perturbation in hemoglobin metabolism following JPC-3210 exposure. The metabolomics data demonstrated a specific depletion of short hemoglobin-derived peptides, peptidomics analysis revealed a depletion of longer hemoglobin-derived peptides, and the hemoglobin fractionation assay demonstrated decreases in hemoglobin, heme and hemozoin levels. To further elucidate the mechanism responsible for inhibition of hemoglobin metabolism, we used in vitro β-hematin polymerization assays and showed JPC-3210 to be an intermediate inhibitor of β-hematin polymerization, about 10-fold less potent then the quinoline antimalarials, such as chloroquine and mefloquine. Further, quantitative proteomics analysis showed that JPC-3210 treatment results in a distinct proteomic signature compared with other known antimalarials. While JPC-3210 clustered closely with mefloquine in the metabolomics and proteomics analyses, a key differentiating signature for JPC-3210 was the significant enrichment of parasite proteins involved in regulation of translation. These studies revealed that the mode of action for JPC-3210 involves inhibition of the hemoglobin digestion pathway and elevation of regulators of protein translation. Importantly, JPC-3210 demonstrated rapid parasite killing kinetics compared with other quinolones, suggesting that JPC-3210 warrants further investigation as a potentially long acting partner drug for malaria treatment.

The life cycle of malaria parasites in both their mammalian host and mosquito vector consists of multiple developmental stages that ensure proper replication and progeny survival. The transition between these stages is fueled by nutrients scavenged from the host and fed into specialized metabolic pathways of the parasite. One such pathway is used by Plasmodium falciparum, which causes the most severe form of human malaria, to synthesize its major phospholipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Much is known about the enzymes involved in the synthesis of these phospholipids, and recent advances in genetic engineering, single-cell RNA-Seq analyses, and drug screening have provided new perspectives on the importance of some of these enzymes in parasite development and sexual differentiation and have identified targets for the development of new antimalarial drugs. This Minireview focuses on two phospholipid biosynthesis enzymes of P. falciparum that catalyze phosphoethanolamine transmethylation (PfPMT) and phosphatidylserine decarboxylation (PfPSD) during the blood stages of the parasite. We also discuss our current understanding of the biochemical, structural, and biological functions of these enzymes and highlight efforts to use them as antimalarial drug targets.

A microbe found in mosquitoes that appears to block malaria could be used to control spread of the disease in humans, according to researchers in Kenya and Britain.

Jena : G. Fischer, 1902.

Wide-scale use of insecticide-treated bed nets has led to substantial declines in global incidences of malaria in recent years. As a result, mosquitos have been shifting their biting times to earlier in the evening and later in the morning. In a new study, an international team of researchers has found that mosquitoes are most likely to transmit malaria in the early evening, when people are exposed, then at midnight, when people are protected by bed nets, or in the morning. The findings may have implications for malaria prevention initiatives.

Malaria parasites invade and replicate within red blood cells (RBCs), extensively modifying their structure and gaining access to the extracellular environment by placing the plasmodial surface anion channel (PSAC) into the RBC membrane. Expression of members of the cytoadherence linked antigen gene 3 (clag3) family is required for PSAC activity, a process that is regulated epigenetically. PSAC is a well-established route of uptake for large, hydrophilic antimalarial compounds and parasites can acquire resistance by silencing clag3 gene expression, thereby reducing drug uptake. We found that exposure to sub-IC50 concentrations of the histone methyltransferase inhibitor chaetocin caused substantial changes in both clag3 gene expression and RBC permeability, reversing acquired resistance to the antimalarial compound blasticidin S that is transported through PSAC. Chaetocin treatment also altered progression of parasites through their replicative cycle, presumably by changing their ability to modify chromatin appropriately to enable DNA replication. These results indicate that targeting histone modifiers could represent a novel tool for reversing epigenetically acquired drug resistance in P. falciparum.

Continuous spread of antimalarial drug resistance is a threat to current chemotherapy efficacy. Therefore, characterizing the genetic diversity of drug resistance markers is needed to follow treatment effectiveness and further update control strategies. Here, we genotyped Plasmodium falciparum resistance gene markers associated with sulfadoxine-pyrimethamine (SP) and artemisinin-based combination therapy (ACT) in isolates from pregnant women in Ghana. The prevalence of the septuple IRNI-A/FGKGS/T pfdhfr/pfdhps haplotypes including the pfdhps A581G and A613S/T mutations was high at delivery among post-SP treatment isolates (18.2%) compared to those of first-antenatal care (before initiation of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP); 6.1%; p = 0.03). Regarding the pfk13 marker gene, two non-synonymous mutations (N458D and A481C) were detected at positions previously related to artemisinin resistance in isolates from Southeast-Asia. These mutations were predicted in silico to alter the stability of the pfk13 propeller-encoding domain. Overall, these findings highlight the need for intensified monitoring and surveillance on additional mutations associated with increased SP resistance as well as emergence of resistance against artemesinin derivatives.

Since 2012, single low dose of primaquine (SLDPQ, 0.25mg/kg) has been recommended with artemisinin-based combination therapies, as first-line treatment of acute uncomplicated Plasmodium falciparum malaria, to interrupt its transmission, especially in low transmission settings of multidrug, including artemisinin, resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and lack of data on its efficacy.

In this randomized controlled trial, 109 Cambodians with acute uncomplicated P. falciparum malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. Transmission-blocking efficacy of SLDPQ was evaluated on Days 0, 1, 2, 3, 7, 14, 21, 28 and recrudescence by reverse transcriptase polymerase chain reaction (RT-PCR) (gametocyte prevalence) and membrane-feeding assays with Anopheles minimus mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP+SLDPQ reduced gametocyte carriage 3 fold compared to DP. Of 48 patients tested on Day 0, only three patients were infectious to mosquitoes (~6%). Post-treatment, three patients were infectious: on D14 (3.5%, 1/29), and on the first and seventh day of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission blocking efficacy.

Our study confirms effective gametocyte clearance of SLDPQ when combined with DP in multidrug resistant P. falciparum and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP and ASMQ-SLDPQ has been deployed to treat all P. falciparum symptomatic patients to further support the elimination of multidrug resistant P. falciparum in Cambodia.

Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicentre trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of piperaquine, estimating a 5.90ms mean QTc-prolongation per 100ng/mL increase in piperaquine concentration. The effect of piperaquine on absolute QTc-interval estimated a mean maximum QTc-interval of 456ms (EC₅₀=209ng/mL). Simulations from the pharmacokinetic-pharmacodynamic models predicted 1.98-2.46% risk of having QTc-prolongation > 60ms in all treatment settings. Although piperaquine administration resulted in QTc-prolongation, no cardiovascular adverse events were found in these patients. Thus, the use of dihydroartemisinin-piperaquine should not be limited by this concern.

A large-scale study in New York looking at the antimalarial drug hydroxychloroquine has cast further doubt on its effectiveness in the treatment of Covid-19 patients.Researchers at Columbia University observed nearly 1,400 patients at a large medical centre in New York City in March and April. They found hydroxychloroquine use led to neither a higher nor lower chance of patients ending up with intubation or death.“Our results cannot completely exclude the possibility of either modest benefit or…

Title: Malaria Parasite Is Infecting, Killing U.S. Baby Deer
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/3/2018 12:00:00 AM

Title: Malaria
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 11/15/2019 12:00:00 AM

ABSTRACT

The protozoan parasites that cause malaria infect a wide variety of vertebrate hosts, including birds, reptiles, and mammals, and the evolutionary pressures inherent to the host-parasite relationship have profoundly shaped the genomes of both host and parasite. Here, we report that these selective pressures have resulted in unexpected alterations to one of the most basic aspects of eukaryotic biology, the maintenance of genome integrity through DNA repair. Malaria parasites that infect humans continuously generate genetic diversity within their antigen-encoding gene families through frequent ectopic recombination between gene family members, a process that is a crucial feature of the persistence of malaria globally. The continuous generation of antigen diversity ensures that different parasite isolates are antigenically distinct, thus preventing extensive cross-reactive immunity and enabling parasites to maintain stable transmission within human populations. However, the molecular basis of the recombination between gene family members is not well understood. Through computational analyses of the antigen-encoding, multicopy gene families of different Plasmodium species, we report the unexpected observation that malaria parasites that infect rodents do not display the same degree of antigen diversity as observed in Plasmodium falciparum and appear to undergo significantly less ectopic recombination. Using comparative genomics, we also identify key molecular components of the diversification process, thus shedding new light on how malaria parasites balance the maintenance of genome integrity with the requirement for continuous genetic diversification.

IMPORTANCE Malaria remains one of the most prevalent and deadly infectious diseases of the developing world, causing approximately 228 million clinical cases and nearly half a million deaths annually. The disease is caused by protozoan parasites of the genus Plasmodium, and of the five species capable of infecting humans, infections with P. falciparum are the most severe. In addition to the parasites that infect people, there are hundreds of additional species that infect birds, reptiles, and other mammals, each exquisitely evolved to meet the specific challenges inherent to survival within their respective hosts. By comparing the unique strategies that each species has evolved, key insights into host-parasite interactions can be gained, including discoveries regarding the pathogenesis of human disease. Here, we describe the surprising observation that closely related parasites with different hosts have evolved remarkably different methods for repairing their genomes. This observation has important implications for the ability of parasites to maintain chronic infections and for the development of host immunity.

ABSTRACT

Coinfections shape immunity and influence the development of inflammatory diseases, resulting in detrimental or beneficial outcome. Coinfections with concurrent Plasmodium species can alter malaria clinical evolution, and malaria infection itself can modulate autoimmune reactions. Yet, the underlying mechanisms remain ill defined. Here, we demonstrate that the protective effects of some rodent malaria strains on T cell-mediated inflammatory pathologies are due to an RNA virus cohosted in malaria-parasitized blood. We show that live and extracts of blood parasitized by Plasmodium berghei K173 or Plasmodium yoelii 17X YM, protect against P. berghei ANKA-induced experimental cerebral malaria (ECM) and myelin oligodendrocyte glycoprotein (MOG)/complete Freund’s adjuvant (CFA)-induced experimental autoimmune encephalomyelitis (EAE), and that protection is associated with a strong type I interferon (IFN-I) signature. We detected the presence of the RNA virus lactate dehydrogenase-elevating virus (LDV) in the protective Plasmodium stabilates and we established that LDV infection alone was necessary and sufficient to recapitulate the protective effects on ECM and EAE. In ECM, protection resulted from an IFN-I-mediated reduction in the abundance of splenic conventional dendritic cell and impairment of their ability to produce interleukin (IL)-12p70, leading to a decrease in pathogenic CD4⁺ Th1 responses. In EAE, LDV infection induced IFN-I-mediated abrogation of IL-23, thereby preventing the differentiation of granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing encephalitogenic CD4⁺ T cells. Our work identifies a virus cohosted in several Plasmodium stabilates across the community and deciphers its major consequences on the host immune system. More generally, our data emphasize the importance of considering contemporaneous infections for the understanding of malaria-associated and autoimmune diseases.

IMPORTANCE Any infection modifies the host immune status, potentially ameliorating or aggravating the pathophysiology of a simultaneous inflammatory condition. In the course of investigating how malaria infection modulates the severity of contemporaneous inflammatory diseases, we identified a nonpathogenic mouse virus in stabilates of two widely used rodent parasite lines: Plasmodium berghei K173 and Plasmodium yoelii 17X YM. We established that the protective effects of these Plasmodium lines on cerebral malaria and multiple sclerosis are exclusively due to this virus. The virus induces a massive type I interferon (IFN-I) response and causes quantitative and qualitative defects in the ability of dendritic cells to promote pathogenic T cell responses. Beyond revealing a possible confounding factor in rodent malaria models, our work uncovers some bases by which a seemingly innocuous viral (co)infection profoundly changes the immunopathophysiology of inflammatory diseases.

Microscopy and rapid diagnostic tests (RDTs) are the main diagnostic tools for malaria but fail to detect low-density parasitemias that are important for maintaining malaria transmission. To complement existing diagnostic methods, an isothermal reverse transcription-recombinase polymerase amplification and lateral flow assay (RT-RPA) was developed. We compared the performance with that of ultrasensitive reverse transcription-quantitative PCR (uRT-qPCR) using nucleic acid extracts from blood samples (n = 114) obtained after standardized controlled human malaria infection (CHMI) with Plasmodium falciparum sporozoites. As a preliminary investigation, we also sampled asymptomatic individuals (n = 28) in an area of malaria endemicity (Lambaréné, Gabon) to validate RT-RPA and assess its performance with unprocessed blood samples (dbRT-RPA). In 114 samples analyzed from CHMI trials, the positive percent agreement to uRT-qPCR was 90% (95% confidence interval [CI], 80 to 96). The negative percent agreement was 100% (95% CI, 92 to 100). The lower limit of detection was 64 parasites/ml. In Gabon, RT-RPA was 100% accurate with asymptomatic volunteers (n = 28), while simplified dbRT-RPA showed 89% accuracy. In a subgroup analysis, RT-RPA detected 9/10 RT-qPCR-positive samples, while loop-mediated isothermal amplification (LAMP) detected 2/10. RT-RPA is a reliable diagnostic test for asymptomatic low-density infections. It is particularly useful in settings where uRT-qPCR is difficult to implement.

Balamuthia mandrillaris is an under-reported, pathogenic free-living amoeba that causes Balamuthia amoebic encephalitis (BAE) and cutaneous skin infections. Although cutaneous infections are not typically lethal, BAE with or without cutaneous involvement is usually fatal. This is due to the lack of drugs that are both efficacious and can cross the blood-brain barrier. We aimed to discover new leads for drug discovery by screening the open-source Medicines for Malaria Venture (MMV) Malaria Box and MMV Pathogen Box, with 800 compounds total. From an initial single point screen at 1 and 10 μM, we identified 54 hits that significantly inhibited the growth of B. mandrillaris in vitro. Hits were reconfirmed in quantitative dose-response assays and 23 compounds (42.6%) were confirmed with activity greater than miltefosine, the current standard of care.

Advances in synthetic biology have enabled the production of a variety of compounds using bacteria as a vehicle for complex compound biosynthesis. Violacein, a naturally occurring indole pigment with antibiotic properties, can be biosynthetically engineered in Escherichia coli expressing its nonnative synthesis pathway. To explore whether this synthetic biosynthesis platform could be used for drug discovery, here we have screened bacterially derived violacein against the main causative agent of human malaria, Plasmodium falciparum. We show the antiparasitic activity of bacterially derived violacein against the P. falciparum 3D7 laboratory reference strain as well as drug-sensitive and -resistant patient isolates, confirming the potential utility of this drug as an antimalarial agent. We then screen a biosynthetic series of violacein derivatives against P. falciparum growth. The varied activity of each derivative against asexual parasite growth points to the need to further develop violacein as an antimalarial. Towards defining its mode of action, we show that biosynthetic violacein affects the parasite actin cytoskeleton, resulting in an accumulation of actin signal that is independent of actin polymerization. This activity points to a target that modulates actin behavior in the cell either in terms of its regulation or its folding. More broadly, our data show that bacterial synthetic biosynthesis could become a suitable platform for antimalarial drug discovery, with potential applications in future high-throughput drug screening with otherwise chemically intractable natural products.

Plasmodium vivax relapse is one of the major causes of sustained global malaria transmission. Primaquine (PQ) is the only commercial drug available to prevent relapses, and its efficacy is dependent on metabolic activation by cytochrome P450 2D6 (CYP2D6). Impaired CYP2D6 function, caused by allelic polymorphisms, leads to the therapeutic failure of PQ as a radical cure for P. vivax malaria. Here, we hypothesized that the host immune response to malaria parasites modulates susceptibility to P. vivax recurrences in association with CYP2D6 activity. We performed a 10-year retrospective study by genotyping CYP2D6 polymorphisms in 261 malaria-exposed individuals from the Brazilian Amazon. The immune responses against a panel of P. vivax blood-stage antigens were evaluated by serological assays. We confirmed our previous findings, which indicated an association between impaired CYP2D6 activity and a higher risk of multiple episodes of P. vivax recurrence (risk ratio, 1.75; 95% confidence interval [CI], 1.2 to 2.6; P = 0.0035). An important finding was a reduction of 3% in the risk of recurrence (risk ratio, 0.97; 95% CI, 0.96 to 0.98; P < 0.0001) per year of malaria exposure, which was observed for individuals with both reduced and normal CYP2D6 activity. Accordingly, subjects with long-term malaria exposure and persistent antibody responses to various antigens showed fewer episodes of malaria recurrence. Our findings have direct implications for malaria control, since it was shown that nonimmune individuals who do not respond adequately to treatment due to reduced CYP2D6 activity may present a significant challenge for sustainable progress toward P. vivax malaria elimination.

We report a systematic, cellular phenotype-based antimalarial screening of the Medicines for Malaria Venture Pathogen Box collection, which facilitated the identification of specific blockers of late-stage intraerythrocytic development of Plasmodium falciparum. First, from standard growth inhibition assays, we identified 173 molecules with antimalarial activity (50% effective concentration [EC₅₀] ≤ 10 μM), which included 62 additional molecules over previously known antimalarial candidates from the Pathogen Box. We identified 90 molecules with EC₅₀ of ≤1 μM, which had significant effect on the ring-trophozoite transition, while 9 molecules inhibited the trophozoite-schizont transition and 21 molecules inhibited the schizont-ring transition (with ≥50% parasites failing to proceed to the next stage) at 1 μM. We therefore rescreened all 173 molecules and validated hits in microscopy to prioritize 12 hits as selective blockers of the schizont-ring transition. Seven of these molecules inhibited the calcium ionophore-induced egress of Toxoplasma gondii, a related apicomplexan parasite, suggesting that the inhibitors may be acting via a conserved mechanism which could be further exploited for target identification studies. We demonstrate that two molecules, MMV020670 and MMV026356, identified as schizont inhibitors in our screens, induce the fragmentation of DNA in merozoites, thereby impairing their ability to egress and invade. Further mechanistic studies would facilitate the therapeutic exploitation of these molecules as broadly active inhibitors targeting late-stage development and egress of apicomplexan parasites relevant to human health.

Researchers studying malaria in Kenya have discovered a microbe that blocks transmission of malaria from mosquitoes which could pave the way to eradicating the disease.

Though it issued an Emergency Use Authorization (EUA) for anti-malaria drugs to treat or prevent coronavirus (COVID-19), the U.S. Food and Drug Administration (FDA) reiterated its warning about the known side effects of hydroxychloroquine and chloroquine, including serious and potentially life-threatening heart rhythm problems.

Today's Daily Dose brings you news about Bristol-Myers' CheckMate -743 study results; Cyclacel Pharma's entry into COVID-19 drug bandwagon; Exelixis touching a new 52-week high and Novartis exploring anti-malaria drug for COVID-19.

Genocea has identified an immunological imprint in patients with malaria and is using a $1.2 million grant from the Gates Foundation to turn the findings into a vaccine.

South Africa announces stimulus plan and a pathway for opening up As of this writing, the African continent has registered over 27,800 COVID-19 cases, with over 1,300 confirmed deaths, according to the Africa Centers for Disease Control and Prevention. Countries around the continent continue to instate various forms of social distancing restrictions: For example, in…

South Africa announces stimulus plan and a pathway for opening up As of this writing, the African continent has registered over 27,800 COVID-19 cases, with over 1,300 confirmed deaths, according to the Africa Centers for Disease Control and Prevention. Countries around the continent continue to instate various forms of social distancing restrictions: For example, in…

South Africa announces stimulus plan and a pathway for opening up As of this writing, the African continent has registered over 27,800 COVID-19 cases, with over 1,300 confirmed deaths, according to the Africa Centers for Disease Control and Prevention. Countries around the continent continue to instate various forms of social distancing restrictions: For example, in…

A rise in cases of the mosquito-borne disease poses another layer of threat in a country where the health system is already struggling

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At least 131 people have died from malaria in Zimbabwe in a new outbreak, adding pressure to a country already struggling to deal with Covid-19.

The fatalities occurred in 201 outbreaks recorded across the country, according to the Ministry of Health. Meanwhile Zimbabwe’s lockdown has been extended by two weeks to prevent the spread of coronavirus.

Related: 'We will starve': Zimbabwe's poor full of misgiving over Covid-19 lockdown

Several African leaders have expressed an interest in a plant-based tonic developed in Madagascar

Among patients given hydroxychloroquine, 32.3% ended up needing a ventilator or dying, compared with 14.9% of patients who were not given the drug

CDC researchers have developed new tools using GPS technology and PDAs to help prevent the spread of malaria in Africa, according to a study published

Tens and thousands of people in India are being affected by mosquito-borne diseases like dengue, malaria and chikungunya. However, dengue and malaria