Do natural catastrophic events and exceptional climatic conditions also affect parasites?

Parasites and parasitologists have always lived together in good and bad luck in a sort of forced marriage. In recent times bad luck certainly prevailed, because of increasing man-made emergencies such as wars, chemical disasters, but also because of natural disasters, amplified by climate change, that condition more and more parasite–host equilibrium. The symposium at the National Congress of the Italian Society for Parasitology, was a first occasion for Italian parasitologists to reason about ‘disaster parasitology’ and researchers’ responsibilities.

Synthesis and biological evaluation of benzhydryl-based antiplasmodial agents possessing Plasmodium falciparum chloroquine resistance transporter (PfCRT) inhibitory activity.

Due to the surge in resistance to common therapies, malaria remains a significant concern to human health worldwide. In chloroquine (CQ)-resistant (CQ-R) strains of Plasmodium falciparum, CQ and related drugs are effluxed from the parasite's digestive vacuole (DV). This process is mediated by mutant isoforms of a protein called CQ resistance transporter (PfCRT).

In vitro Multistage Malaria Transmission Blocking Activity of Selected Malaria Box Compounds.

Purpose: Continuous efforts into the discovery and development of new antimalarials are required to face the emerging resistance of the parasite to available treatments. Thus, new effective drugs, ideally able to inhibit the life-cycle stages that cause the disease as well as those responsible for its transmission, are needed. Eight compounds from the Medicines for Malaria Venture (MMV) Malaria Box, potentially interfering with the parasite polyamine biosynthesis were selected and assessed in vitro for activity against malaria transmissible stages, namely mature gametocytes and early sporogonic stages.

A murine malaria protocol for characterizing transmission blocking benefits of antimalarial drug combinations.

Background: Current efforts towards malaria elimination include the discovery of new transmission blocking (TB) drugs and identification of compounds suitable to replace primaquine, recommended as transmission blocking post treatment after artemisinin combination therapy (ACT). High through put screening of compound libraries has allowed to identify numerous compounds active against gametocytes and insect early sporogonic stages, but few studies have been performed to characterize TB compounds . Here we propose a double TB drug Direct Feeding Assay (2TB-DFA), suitable to assess the combined effects of TB compounds.

Plasmodium stage-selective antimalarials from Lophira lanceolata stem bark.

Targeting the transmissible stages of the Plasmodium parasite that develop in the human and mosquito host is a crucial strategy for malaria control and elimination. Medicinal plants offer a prolific source for the discovery of new antimalarial compounds. The recent identification of the gametocytocidal activity of lophirone E, obtained from the African plant Lophira lanceolata (Ochnaceae), inspired the evaluation of the plant also against early sporogonic stages of the parasite development.

Identification of a potent and selective gametocytocidal antimalarial agent from the stem barks of Lophira lanceolata.

Bioassay-guided fractionation of the organic extract obtained from stem barks of the African plant Lophira lanceolata has led to the isolation of seven biflavonoids, including the new α'-chlorolophirone E (5) and 5'-chlorolophirone D (6). Among the isolated compounds, the bichalcone lophirone E was identified as a potent gametocytocidal agent with an IC value in the nanomolar range and negligible cytotoxicity (selectivity index = 570). Lophirone E proved to be about 100 times more active against P.

Adenosine Triphosphate-Binding Cassette Transporters Are Not Involved In the Detoxification of Extracts In Larvae.

Detoxifying pathways of mosquitoes against the neem () extracts are still unclear. The aim of the present study was to investigate the role of adenosine triphosphate-binding cassette (ABC) transporters in this process in , one of the main malaria vectors in southern Asia. Third-stage larvae of were fed with fish food alone or in combination with neem extract at 0.

Exploring communities' and health workers' perceptions of indicators and drivers of malaria decline in Malindi, Kenya.

Background: Since 2000, a decrease in malaria burden has been observed in most endemic countries. Declining infection rates and disease burden and reduction in asymptomatic carriers are the outcome of improved quality of care and related health system factors. These include improved case management through better diagnosis, implementation of highly effective antimalarial drugs and increased use of bednets.

A formative study of disposal and re-use of old mosquito nets by communities in Malindi, Kenya.

Background: About 30 million insecticide treated mosquito nets have been distributed in Kenya since 2001 and ownership is approaching full coverage. As a consequence of this achievement, Kenya is faced with the challenge of disposing old mosquito nets that are no longer in use. The study aimed at investigating ways of disposal and re-use of old and torn nets by end users.

Daucovirgolides I-L, four congeners of the antimalarial daucovirgolide G from Daucus virgatus.

Repeated chromatographic purifications of aerial parts of the Tunisian plant Daucus virgatus led to the isolation of four new germacranolides, named daucovirgolides I-L (2-5), along with the Plasmodium transmission-blocking agent daucovirgolide G. The chemical structures of the new compounds were defined as mono- or di-angeloylated germacrane-type sesquiterpenoids by spectroscopic (mainly 1D and 2D NMR) and spectrometric methods (ESIMS). The low potency exhibited by daucovirgolides I-L further supports the observation that strict structural requirements do exist for the Plasmodium transmission blocking activity in the daucovirgolide series.

Effects of Azadirachta indica seed kernel extracts on early erythrocytic schizogony of Plasmodium berghei and pro-inflammatory response in inbred mice.

Background: Medicinal plant research may contribute to develop new pharmacological control tools for vector borne diseases, such as malaria.

Methods: The effects of methanol extracts (ME) obtained from seed kernel of ripe and unripe Azadirachta indica fruits were studied on erythrocytic proliferation of the rodent malaria parasite Plasmodium berghei strain ANKA and on mice pro-inflammatory response, as evaluated by measuring the matrix-metalloproteinase-9 (MMP-9) and tumour necrosis factor (TNF) plasma levels, in two mouse strains (C57BL/6 and BALB/c) which are considered as prototypical of Th1 and Th2 immune response, respectively.

Results: ME obtained from seed kernel of unripe Azadirachta indica fruits decreased by about 30% the proportion of erythrocytes infected with the malaria parasite in C57BL/6 mice in the 4 days suppressive test.

Impact of honey on dental erosion and adhesion of early bacterial colonizers.

The aim was to investigate if honey causes erosion and if salivary pellicle modified with honey, or its components, or the by-product propolis has a protective effect against dental erosion and adhesion of early bacterial colonizers. The tested substances were: 3 types of honey, methylglyoxal (MGO), hydrogen peroxide, propolis. First in the erosion experiment, 120 human enamel specimens were covered with salivary pellicle and modified with the substances.

In Vivo and In Vitro Activities and ADME-Tox Profile of a Quinolizidine-Modified 4-Aminoquinoline: A Potent Anti-P. falciparum and Anti-P. vivax Blood-Stage Antimalarial.

Natural products are a prolific source for the identification of new biologically active compounds. In the present work, we studied the in vitro and in vivo antimalarial efficacy and ADME-Tox profile of a molecular hybrid (AM1) between 4-aminoquinoline and a quinolizidine moiety derived from lupinine (). The aim was to find a compound endowed with the target product profile-1 (TCP-1: molecules that clear asexual blood-stage parasitaemia), proposed by the Medicine for Malaria Venture to accomplish the goal of malaria elimination/eradication.

Angeloylated Germacranolides from Daucus virgatus and Their Plasmodium Transmission Blocking Activity.

Phytochemical investigation of the aerial parts of the Tunisian plant Daucus virgatus led to the isolation of eight new germacranolides named daucovirgolides A-H (1-8). The stereostructures of these sesquiterpene lactones, decorated by either one or two angeloyl groups, have been determined by a combination of MS, NMR spectroscopy, chemical derivatization, and comparison of experimental electronic circular dichroism curves with TDDFT-predicted data. Daucovirgolide G (7) proved to be the single member of this family to possess a marked inhibitory activity (92% at 50 μg/mL) on the development of Plasmodium early sporogonic stages, the nonpathogenic transmissible stages of malaria parasites, devoid of general cytotoxicity.

In vitro and ex vivo activity of an Azadirachta indica A.Juss. seed kernel extract on early sporogonic development of Plasmodium in comparison with azadirachtin A, its most abundant constituent.

Background: NeemAzal (NA) is a quantified extract from seed kernels of neem, Azadirachta indica A.Juss. (Meliaceae), with a wide spectrum of biological properties, classically ascribed to its limonoid content.

Novel metalloantimalarials: Transmission blocking effects of water soluble Cu(I), Ag(I) and Au(I) phosphane complexes on the murine malaria parasite Plasmodium berghei.

The water soluble phosphane complexes [M(L)]PF (M=Cu(I), Ag(I)) and [Au(L)]Cl (L=thp (tris(hydroxymethyl)phosphane) or PTA (1,3,5-triaza-7-phosphaadamantane)) showed notable in vitro activity against Plasmodium early sporogonic stages, the sexual forms of the malaria parasite that are responsible for infection of the mosquito vector. Effects varied according to both, the type of metal and phosphane ligands. [Ag(thp)]PF was the best performing complex exhibiting a half inhibitory concentration (IC) value in the low micromolar range (0.

Transmission blocking effects of neem (Azadirachta indica) seed kernel limonoids on Plasmodium berghei early sporogonic development.

Azadirachta indica, known as neem tree and traditionally called "nature's drug store" makes part of several African pharmacopeias and is widely used for the preparation of homemade remedies and commercial preparations against various illnesses, including malaria. Employing a bio-guided fractionation approach, molecules obtained from A. indica ripe and green fruit kernels were tested for activity against early sporogonic stages of Plasmodium berghei, the parasite stages that develop in the mosquito mid gut after an infective blood meal.

Neemazal ® as a possible alternative control tool for malaria and African trypanosomiasis?

Background: Research efforts to identify possible alternative control tools for malaria and African trypanosomiasis are needed. One promising approach relies on the use of traditional plant remedies with insecticidal activities.

Methods: In this study, we assessed the effect of blood treated with different doses of NeemAzal ® (NA, neem seed extract) on mosquitoes (Anopheles coluzzii) and tsetse flies (Glossina palpalis gambiensis) (i) avidity to feed on the treated blood, (ii) longevity, and (iii) behavioural responses to human and calf odours in dual-choice tests.

Plasmodium transmission blocking activities of Vernonia amygdalina extracts and isolated compounds.

Background: Medicinal plants are a validated source for discovery of new leads and standardized herbal medicines. The aim of this study was to assess the activity of Vernonia amygdalina leaf extracts and isolated compounds against gametocytes and sporogonic stages of Plasmodium berghei and to validate the findings on field isolates of Plasmodium falciparum.

Methods: Aqueous (Ver-H2O) and ethanolic (Ver-EtOH) leaf extracts were tested in vivo for activity against sexual and asexual blood stage P.

Poly-Electrophilic Sesquiterpene Lactones from Vernonia amygdalina: New Members and Differences in Their Mechanism of Thiol Trapping and in Bioactivity.

In addition to known compounds, the leaves of Vernonia amygdalina afforded the new sesquiterpene lactones 14-O-methylvernolide (2), 3'-deoxyvernodalol (6), and vernomygdalin (8). These and related compounds were evaluated for modulation of a series of thiol trapping-sensitive transcription factors (NF-κB, STAT3, and Nrf2), involved in the maintenance of the chronic inflammatory condition typical of human degenerative diseases. Vernolide (1) emerged as a potent inhibitor of STAT3 and NF-κB and showed cytostatic activity toward the prostate cancer cell line DU45, arresting the cell cycle at the S phase.

Salinomycin and other ionophores as a new class of antimalarial drugs with transmission-blocking activity.

The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual stages of Plasmodium, thus with both curative and transmission-blocking activities. The aim of the present work was to investigate whether the class of monovalent ionophores, which includes drugs used in veterinary medicine and that were recently proposed as human anticancer agents, meets these requirements. The activity of salinomycin, monensin, and nigericin on Plasmodium falciparum asexual and sexual erythrocytic stages and on the development of the Plasmodium berghei and P.

Impact of repeated NeemAzal-treated blood meals on the fitness of Anopheles stephensi mosquitoes.

Background: Herbal remedies are widely used in many malaria endemic countries to treat patients, in particular in the absence of anti-malarial drugs and in some settings to prevent the disease. Herbal medicines may be specifically designed for prophylaxis and/or for blocking malaria transmission to benefit both, the individual consumer and the community at large. Neem represents a good candidate for this purpose due to its inhibitory effects on the parasite stages that cause the clinical manifestations of malaria and on those responsible for infection in the vector.

Enabling factors facilitating the use of neem-based remedies for the management of malaria in the Lower Shire District of Chikwawa, Malawi.

Background: Malaria remains a major public health threat in Malawi, affecting mostly children under five and pregnant women. Despite the availability of chemotherapy and chemoprophylaxis, resistance to sulfadoxine pyrimethamine and the high cost and complicated regimen of artemether-lumefantrine have accelerated the use of home-based remedies for the management of malaria in Chikwawa district, Malawi. This study aimed to determine factors that facilitate the use of herbal remedies within communities in the management of malaria in the presence of free health care services, with the intention of assessing the feasibility of developing improved herbal products as anti-malarial prophylaxis.

A retrospective evaluation of the quality of malaria case management at twelve health facilities in four districts in Zambia.

Objective: To establish the appropriateness of malaria case management at health facility level in four districts in Zambia.

Methods: This study was a retrospective evaluation of the quality of malaria case management at health facilities in four districts conveniently sampled to represent both urban and rural settings in different epidemiological zones and health facility coverage. The review period was from January to December 2008.

A user friendly method to assess Anopheles stephensi (Diptera: Culicidae) vector fitness: fecundity.

Fecundity, bloodmeal size, and survival are among the most important parameters in the overall fitness of mosquitoes. Impact of an intervention that affects fecundity can be assessed by directly counting the eggs laid by exposed mosquitoes, which is usually done manually. We have developed a macroinstruction, which can be used to count thousands of Anopheles stephensi Liston eggs in a few minutes, to provide an alternative and adaptable method to egg counting as a measure of fecundity.