A study of the anti-plasmodium activity of angiotensin II analogs

Controlling the dissemination of malaria requires the development of new drugs against its etiological agent, a protozoan of the Plasmodium genus. Angiotensin II and its analog peptides exhibit activity against the development of immature and mature sporozoites of Plasmodium gallinaceum. In this study, we report the synthesis and characterization of angiotensin II linear and cyclic analogs with anti-plasmodium activity. The peptides were synthesized by a conventional solid-phase method on Merrifield's resin using the t-Boc strategy, purified by RP-HPLC and characterized by liquid chromatography/ESI (+) MS (LC-ESI(+)/MS), amino acid analysis, and capillary electrophoresis. Anti-plasmodium activity was measured in vitro by fluorescence microscopy using propidium iodine uptake as an indicator of cellular damage. The activities of the linear and cyclic peptides are not significantly different (p < 0.05). Kinetics studies indicate that the effects of these peptides on plasmodium viability overtime exhibit a sigmoidal profile and that the system stabilizes after a period of 1 h for all peptides examined. The results were rationalized by partial least-square analysis, assessing the position-wise contribution of each amino acid. The highest contribution of polar amino acids and a Lys residue proximal to the C-terminus, as well as that of hydrophobic amino acids in the N-terminus, suggests that the mechanism underlying the anti-malarial activity of these peptides is attributed to its amphiphilic character.

A research agenda for malaria eradication: basic science and enabling technologies

Today's malaria control efforts are limited by our incomplete understanding of the biology of Plasmodium and of the complex relationships between human populations and the multiple species of mosquito and parasite. Research priorities include the development of in vitro culture systems for the complete life cycle of P. falciparum and P. vivax and the development of an appropriate liver culture system to study hepatic stages. In addition, genetic technologies for the manipulation of Plasmodium need to be improved, the entire parasite metabolome needs to be characterized to identify new druggable targets, and improved information systems for monitoring the changes in epidemiology, pathology, and host-parasite-vector interactions as a result of intensified control need to be established to bridge the gap between bench, preclinical, clinical, and population-based sciences.

Frequency of Malaria and Glucose-6-phosphate Dehydrogenase Deficiency in Tajikistan

Background During the Soviet era, malaria was close to eradication in Tajikistan. Since the early 1990s, the disease has been on the rise and has become endemic in large areas of southern and western Tajikistan. The standard national treatment for Plasmodium vivax is based on primaquine. This entails the risk of severe haemolysis for patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Seasonal and geographical distribution patterns as well as G6PD deficiency frequency were analysed with a view to improve understanding of the current malaria situation in Tajikistan. Methods Spatial and seasonal distribution was analysed, applying a risk model that included key environmental factors such as temperature and the availability of mosquito breeding sites. The frequency of G6PD deficiency was studied at the health service level, including a cross-sectional sample of 382 adult men. Results Analysis revealed high rates of malaria transmission in most districts of the southern province of Khatlon, as well as in some zones in the northern province of Sughd. Three categories of risk areas were identified: (i) zones at relatively high malaria risk with high current incidence rates, where malaria control and prevention measures should be taken at all stages of the transmission cycle; (ii) zones at relatively high malaria risk with low current incidence rates, where malaria prevention measures are recommended; and (iii) zones at intermediate or low malaria risk with low current incidence rates where no particular measures appear necessary. The average prevalence of G6PD deficiency was 2.1% with apparent differences between ethnic groups and geographical regions. Conclusion The study clearly indicates that malaria is a serious health issue in specific regions of Tajikistan. Transmission is mainly determined by temperature. Consequently, locations at lower altitude are more malaria-prone. G6PD deficiency frequency is too moderate to require fundamental changes in standard national treatment of cases of P. vivax.

Primaquine-induced differential gene expression analysis in mice liver using DNA microarrays

Primaquine (PQ). a clinically important derivative of 8-aminoquinoline used against the hepatic stages (hypnozoites) of Plasmodium vivax and Plasmodium ova Ie. was studied to evaluate and compare between mRNA expression. and biochemical and histological parameters of hepatic stress in adult Swiss mice (Mus musculus). Following single oral dose of PQ (40 mglkg. bw). alanine aminotransferase (ALT) and aspartate aminotransferase (AST) along with hematoxylin and eosin stained liver sections did not show any signs of hepatic stress at 6. 12 and 24 h except for ALT activity at 6 h. However. analysis at RNA transcript level revealed consistent and significant deregulation (p<0.01 and twofold) of 16 probes corresponding to important cellular processes such as protein transportation. transcription regulation. intracellular signaling. protein synthesis, hematopoiesis, cell adhesion and cell proliferation. Pathway analysis identified large number of affected genes corresponding to 40 Gene Ontology terms having a z score greaibr than 2. These results indicate that PQ at high doses may affect gene expression in liver and may produce undesirable outcomes if consumed for longer durations.

Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene.

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P = 3.8 x 10(-5)), establishing a novel phenotype for this genetic variant.

Isolation of multiple sequences from the Plasmodium falciparum genome that encode conserved domains homologous to those in erythrocyte-binding proteins.

Open reading frames in the Plasmodium falciparum genome encode domains homologous to the adhesive domains of the P. falciparum EBA-175 erythrocyte-binding protein (eba-175 gene product) and those of the Plasmodium vivax and Plasmodium knowlesi Duffy antigen-binding proteins. These domains are referred to as Duffy binding-like (DBL), after the receptor that determines P. vivax invasion of Duffy blood group-positive human erythrocytes. Using oligonucleotide primers derived from short regions of conserved sequence, we have developed a reverse transcription-PCR method that amplifies sequences encoding the DBL domains of expressed genes. Products of these reverse transcription-PCR amplifications include sequences of single-copy genes (including eba-175) and variably transcribed genes that cross-hybridize to multiple regions of the genome. Restriction patterns of the multicopy genes show a high degree of polymorphism among different parasite lines, whereas single-copy genes are generally conserved. Characterization of the single-copy genes has identified a gene (ebl-1) that is related to eba-175 and is likely to be involved in erythrocyte invasion.

Revisão taxonômica e filogenia da Seção Myzorhynchella de Anopheles (Nyssorhynchus) (Diptera: Culicidae)

Anopheles é o gênero da família Culicidae mais estudado devido sua importância médica. Atualmente o gênero Anopheles compreende 472 espécies válidas que estão divididas em sete subgêneros. Os principais vetores de plasmódio da Malária no Brasil pertencem ao subgênero Nyssorhynchus, que inclui 39 espécies oficialmente reconhecidas e um número crescente de complexos de espécies crípticas que estão distribuídas em três Seções: Myzorhynchella, Albimanus e Argyritarsis. Atualmente a Seção Myzorhynchella é formada por seis espécies: An. lutzii, An. parvus, An. nigritarsis, An. guarani, An. antunesi e An. pristinus. Para o desenvolvimento da análise morfológica, observou-se material-tipo depositado em diferentes coleções, espécimes depositados na coleção entomológica da FSP/USP, além de outros obtidos em coletas realizadas durante o presente estudo em diferentes localidades do Brasil. As análises moleculares foram desenvolvidas a partir de espécimes obtidos nas coletas. Revisão taxonômica da Seção Myzorhynchella é apresentada, incluindo-se descrições de quatro novas espécies e redescrições das demais, informações sobre bionomia, importância médica, caracterização molecular, distribuição geográfica, estado de preservação do material-tipo, além de chaves de identificação de adultos, larva de quarto estádio e genitália masculina. Os resultados das análises filogenéticas utilizando sequências de ITS2, COI e Catalase indicam a existência de pelo menos doze espécies dentro da Seção Myzorhynchella, os espécimes que vêm sendo identificados como An. antunesi constitui um complexo formado por possíveis cinco espécies e aqueles de An. parvus e An. pristinus também podem representar complexos de espécies. As sequências de ITS2 podem ser utilizadas como marcador diagnóstico para espécies da Seção Myzorhynchella. Contudo, o estudo ainda demonstra que pouco se conhece sobre a diversidade de espécies de Anopheles que ocorrem em ambientes onde a malária ocorre em baixa endemicidade. Pelo número de espécies novas encontradas e pela escassez de trabalhos com espécies da Seção, fica evidente a necessidade de mais estudos.

Can iron be used to treat malaria?

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Studies on Brazilian anophelines from the northeast and Amazon regions ...

"References" at end of each study.

New haplotypes of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene among chloroquine-resistant parasite isolates

Mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene were examined to assess their associations with chloroquine resistance in clinical samples from Armopa (Papua) and Papua New Guinea. In Papua, two of the five pfcrt haplotypes found were new: SVIET from Armopa and CVIKT from an isolate in Timika. There was also a strong association (P < 0.0001) between the pfcrt 76T allele and chloroquine resistance in 50 samples. In Papua New Guinea, mutations in the pfcrt gene were observed in 15 isolates with chloroquine minimum inhibitory concentrations (MICs) of 16-64 pmol, while the remaining six isolates, which had a wild-type pfcrt gene at codon 76, had MICs of 2-8 pmol. These observations confirm that mutations at codon 76 in the pfcrt gene are present in both in vivo and in vitro cases of chloroquine resistance, and that detection of the pfcrt 76T allele could predict potential chloroquine treatment failures.

Detection and differentiation of Plasmodium species by polymerase chain reaction and colorimetric detection in blood samples of patients with suspected malaria

Polymerase chain reaction (PCR) is now recognized as a sensitive and specific method for detecting Plasmodium species in blood. In this Study. we tested 279 blood samples, from patients with Suspected malaria, by a PCR assay utilizing species-specific colorimetric detection. and compared the results to light microscopy. Overall, both assays were in agreement for 270 of the 279 specimens. P. vivax was detected in 131 (47.0%) specimens. P. falciparum in 64 (22.9%) specimens, P. ovale in 6 (2.1%) specimens, and P. malariae in 5 (1.8%) specimens. Both P. falciparum and P. vivax were detected in a further 10 (3.6%) specimens, and 54 (19.3%) specimens were negative by both assays. In the remaining nine specimens, microscopy either failed to detect the parasite or incorrectly identified the species present. In summary, the sensitivity, specificity and simplicity of the PCR assay makes it particularly suitable for use in a diagnostic laboratory. (C) 2004 Elsevier Inc. All rights reserved.

Short report: Lack of sex effect on the pharmacokinetics of primaquine

The pharmacokinetics of primaquine have been well defined in male volunteers, but there is little data on the disposition of the drug in women. We compared the kinetics of primaquine in nine male and nine female healthy Australian volunteers after the administration of a single oral dose (30 mg base) of primaquine. No statistical differences were observed in the following kinetic parameters of primaquine between men and women, respectively: maximum plasma concentration (93 +/- 26 and 115 +/- 38 ng/mL; 95% confidence interval [CI] of the mean difference: -55 to 10 ng/mL; P = 0.16), area under the curve (1.1 +/- 0.5 and 1.2 +/- 0.4 mu g.h/mL; 95% CI: -0.6 to 0.3 mu g.h/mL; P = 0.54), and clearance (0.34 +/- 0.12 and 0.39 +/- 0.14 L/h/kg; 95% CI: -0.17 to 0.08 L/h/kg; P = 0.46). The clinical relevance of such findings would suggest that sex does not have to be taken into account as a factor when prescribing primaquine for radical cure or terminal prophylaxis of Plasmodium vivax malaria.

Új vektoriális betegségek megjelenésének lehetősége, és a már őshonos betegségek jelentőségének növekedése a klímaváltozás következtében. A XXI. század egészségügyi és hadászati biztonságát fenyegető hazardok

Az ízeltlábúak által terjesztett fertőző betegségek egyre emelkedő mértékben jelentenek majd veszélyt Európa mérsékelt övi lakosságának egészségi állapotára nézve. A klímaváltozás következtében meghosszabbodó vegetációs időszak, és az emelkedő átlaghőmérséklet a már jelen lévő betegség (Pl. Lyme), és számos, a lakosság számára új, meleg égövi betegség megtelepedését, vagy újra megjelenését okozhatja, mint amilyen például a leishmaniasis vagy a malária. A jövőben nem csak a civil lakosság egészségi állapotát, de a hadsereg személyi állományának egészségét és a hadműveletek biztonságát is veszélyeztethetik a vektoriális megbetegedések. _____ Emerging vectorial diseases threaten the population of the temperate areas of Europe. Due to climate change the increasing seasonal mean temperatures and the prolongation of the potential activity period of arthropod vectorial organisms will enhance the importance of the tick-borne diseases (eg. Lyme disease) and will facilitate the expansion of new or re-emerging vectorial diseases, such as leishmaniasis or malaria. These serious vectorial diseases can cause notable hazard not only for citizens but for the personnels and may endanger the safety of the operations, too.

Gestão de resíduos sólidos domiciliares na cidade de Chibuto, província de Gaza Moçambique

This study analyzes the process of generation and management of solid waste in the Municipality of the City of Chibuto-Mozambique, drawing on the different approaches towards allocation and the socio-environmental implications resulting from this process and waste spatial distribution. To answer these objectives a questionnaire was administered to 367 households distributed in 14 neighborhoods of the city to elicit information on how solid waste is treated and what could be its impact on public health of the residents. From this perspective, the questionnaire gasp information from immigrant residents regarding both their origin, and socio economic condition. Apart from the questionnaire, semi-structured interviews were conducted to staff working on the Sanitation Sector, Urbanization Sector of the Chibuto Municipality, including the Health Service, and Women and Social Affairs. In addition to these data collection methods, for further discussion on the subject, the researcher draw a theoretical framework grounded through literature review, as well as systematic observation of the phenomenon. Research findings revealed that the solid waste collection services provided by the Chibuto Municipality do not follow the procedures laid down in the Regulation on Solid Waste Management, which advocates environmentally safe, sustainable, and complete management of waste. First, the services use open dumps for waste management. Secondly, waste collection does not cover all citizens living in the neighborhoods governed by the municipality, due to financial, technical, and organizational reasons. More importantly, the study found that due to this failure, more than 90% of households surveyed continue to use the traditional methods on waste management which include burning, or the burial techniques. On the other hand, some citizens throw waste on the streets, a method that threatens public health because it increases cases of diseases related to sanitation problems such as (diarrhea and malaria), especially in suburban and peripheral urban areas. Concerning with the above mentioned problems which constitute a real threat to the public health, some ways are proposed for more sustainable and spatially appropriate solid waste management through recycling, waste sorting, composting, reuse, and reduction of solid waste generation.

A organização da educação no território federal do Amapá: do "ideal" ao real, do liberal ao conservador (1943-1958)

The present study on “organization education on Amapá’s Federal Territory (1943-1958)”, looked forward to answering the following questions: Was there an educational policy, in a systemic way, on the former Amapá’s federal territory? On the other hand, what were the main initiatives of the first intervenors for the education dissemination? After facing these questions, we established, as hypothesis, that the developed actions in the education’s scope on that territory back in the 40’s and 50’s were not able to implant an educational project in Amapá, since there was no preoccupation to understanding the sociocultural reality of Amapá’s population. Given this hypothesis, we analyzed the relation between the political practices developed by the first intervenor on the territory and the brazilian political scenario, from the legal-administrative nature of the federal entities and political conjuncture of the “New State” (1937-1945). To achieve that, we sought some similarities between Janary Gentil Nunes’s ways of governing and Getúlio Vargas’s political actions. To make this happen, it was necessary to check official documents out, as well as unofficial ones, especially the old articles published by “Amapá”, the local newspaper, official press tool back then, which disseminated the beliefs and values of the constituted authorities, with the purpose of “strengthen” the “modernization” ideal on the people. Such practice was based on the attempt of breaking off sociocultural economic backwardness of the territory, hiding out the reality of the Amapá’s population, marked by poverty, a high illiteracy rate and the typical tropical diseases from Amazon (Malaria). During the rupture’s process between the old and the modern, the education takes on a major role in the official speech, being used as political advertisement and as essential element to the modernization and to the development of a “new man”: now “civilized”. However, the investigation on the expansion of the elementary education in Amapá, showed us the presence of a significant number of rural schools, in contradiction to the disseminated urban modernization promise around there. In this sense, we can affirm that educational policy on Amapá’s territory failed by reasons of being based on the “transplantation” of the Federal District’s educational project, and it is important to recall that, back then, the brazilian Federal District was Rio de Janeiro. Despite the public agents had established uncountable schools on rural areas, these were not carried out from a more systemic process, this is, considering the reality of the Amazon’s "cabloco". So, we observed the existence of the separation between the modern speech and the maintenance of old oligarchic practices by that time.