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Lo spazio pubblico è sempre stato considerato un requisito necessario della struttura urbana come elemento centrale per una rigenerazione dell'abitare nella città contemporanea. Si radica all'interno del duplice significato che lega la dimensione fisica dello spazio, dando corpo e forma alla città, alla dimensione sociale e relazionale degli individui che ne determinano la vita. Le diverse forme di socialità, d'organizzazione e d'uso di questi spazi nelle città, sono influenzate sia dai segni che dalle architetture generatrici degli spazi stessi, ma soprattutto dai processi sociali d'identificazione e d'auto-organizzazione nel territorio, in cui il valore dell'abitare è come base della forma dello spazio e della relazione forma-funzione e come relazione culturale e dinamica.

Pyrimethamine, in combination with sulfadoxine, is currently one of the major alternative drugs used for the treatment of chloroquine-resistant #Plasmodium falciparum$ malaria infections in Africa. The mechanism of pyrimethamine resistance has been strongly associated with a single, key point mutation in the dihydrofolate reductase-thymidylate synthase gene, resulting in the substitution of the wild-type allele Ser-108 by either Asn-108 or Thr-108. The pyrimethamine-resistant phenotype and/or genotype were determined in 273 Cameroonian clinical isolates obtained in Yaounde by in vitro assays and polymerase chain reaction-restriction fragment length polymorphism over a 5-year period. The in vitro assays showed that 42% (18 of 43) and 63% (69 of 110) of the isolates obtained in 1994-1995 and 1997-1998, respectively, were resistant to pyrimethamine (50% inhibitory concentration (IC50) is greater than 100 nM). The polymerase chain reaction showed that 43% (55 of 127) and 59% (50 of 85) of the isolates in 1994-1995 and 1997-1998, respectively, had the mutant Asn-108 allele. The pyrimethamine-resistant genotype (Asn-108) corresponded with the pyrimethamine-resistant phenotype (IC50 is greater than or equal to 100 nM) in a large majority (greater than 95%) of the isolates. The results of our study suggest an increasing prevalence of pyrimethamine resistance in Yaounde. Our study further suggests that pyrimethamine resistance can be monitored by a technique that can be adopted by malaria research centers in Africa. (Résumé d'auteur)

A novel #Plasmodium falciparum$ gene, denoted cg2 gene, has been recently discovered, and a distinct genotype, characterized by 12 point mutations and 3 size polymorphisms, has been shown to be associated with chloroquine resistance in laboratory-adapted parasite strains. One of the polymorphic regions, denoted the omega region, consists of 16 tandem repeat units in chloroquine-resistant strains, while the chloroquine-sensitive strains have either less than or equal to 15 or greater than or equal to 17 repeat units. In this study, the in vivo and in vitro responses were compared with the number of repeat units in the omega region of the cg2 gene for 75 Cameroonian isolates determined either by DNA sequencing or agarose gel electrophoresis. The 16-repeat units that characterise the resistant strains were found in 10 chloroquine-sensitive isolates (50% inhibitory concentration (IC50) is less than 100 nM) and 30 chloroquine-resistant isolates (IC50 is greater than or equal to 100 nM). Thirty-five isolates (28 chloroquine-sensitive isolates and 7 chloroquine-resistant isolates) displayed less than or equal to 15 or greater than or equal to 17 repeat units. Of the 18 patients (11 with isolates carrying 16 repeat units and 17 with isolates carrying less than or equal to 15 or greater than or equal to 17 repeat units) showed an adequate clinical response. The sensitivity, specificity, and predictive value were 81% (83%), 74% (61%), and 75% (58%), respectively compared with in vitro (or in vivo) responses. Neither the level of IC50 nor the key #P. falciparum$ multidrug resistance gene (pfmdr 1) allele at position 86 was associated with the number of omega repeat units... (D'après résumé d'auteur)

The in vitro activities of dihydroartemisinin (the biologically active metabolite of artemisinin derivatives), chloroquine, monodesethylamodiaquine (the biologically active metabolite of amodiaquine), quinine, mefloquine, halofantrine, and pyrimethamine were assessed in 65 African isolates of #Plasmodium falciparum$ from Yaoundé, Cameroon using an isotopic microtest. The 50% inhibitory concentration (IC50) values for dihydroartemisinin were within a narrow range from 0.25 to 4.56 nM, with a geometric mean of 1.11 nM (95%) confidence interval = 0.96-1.28 nM). Dihydroartemisinin was equally active (P is greater than 0.05) against the chloroquine-sensitive isolates (geometric mean IC50 = 1.25 nM, 95% confidence interval ) 0.99-157 nM) and the chloroquine-resistant isolates (geometric mean IC50 = 0.979 nM, 95% confidence interval = 0.816-1.18 nM). A significant positive correlation was observed between the responses to dihydroartemisinin and mefloquine (r - 0.662) or halofantrine (r = 0.284), suggesting in vitro cross-resistance. There was no correlation between the responses to dihydroaertemisinin and other antimalarial drugs. ((Résumé d'auteur)

Resistance to antifolate antimalarial drugs (cycloguanil, a biologically active metabolite of proguanil, and pyrimethamine) is associated with a Ser- to Asn-108 point mutation in the dihydrofolate reductase thymidylate synthase gene of #Plasmodium falciparum$. The frequency of this mutation was studied in 127 clinical isolates obtained in Yaounde, Cameroon using a simple and rapid molecular technique based on the polymerase chain reaction and restriction fragment lengh polymorphism. Of the 127 isolates, pure wild-type Ser-108 codon, pure mutant-type Asn-108 codon, and mixed codons were observed in 66, 55, and six parasites, respectively. The proportion of antifolate-resistant, pure mutant-type codon, with respect to pure wild-type or mixed alleles, was 43% (55 to 127). The results of the molecular assay were compared with those of semimicro isotopic in vitro assay in 34 isolates. All 17 pure Ser-108 isolates and two isolates with mixed alleles were sensitive to both pyrimethamine (50% inhibitory concentration [IC50] < 100 nM) and cycloguanil (IC50 < 50 nM). Fourteen of 15 isolates with the mutant-type Asn-108 codon were resistant to pyrimethamine and cycloguanil. One isolate with Asn-108 showed a slightly elevated pyrimethamine IC50 (78 nM), which was within the sensitive range. This study provides further evidence that antifolate-resistant #P. falciparum$ isolates are already present in Yaounde, Cameroon. (Résumé d'auteur)

Polymorphism of the circumsporozoite protein (CSP) of #Plasmodium malariae$ was characterized by comparing gene sequences of twelve field isolates obtained in Yaoundé, Cameroon, Central Africa, and one clinical isolate originating from Côte d'Ivoire, West Africa. The length of the CSP gene ranged from 1266 to 1302 bp. The size polymorphism was due to variation in the number of tandem repeat units. All #P. malariae$ isolates displayed a highly conserved 5' non-repeat region. Seven non-synonymous and two synonymous nucleotide variations were observed in the 3' non-repeat region. In the deduced amino acid sequence the repetitive sequences consisted of a varying number of major (Asn Ala Ala Gly (NAAG) ; range between 42 and 46 units) and minor (Asn Asp Ala Gly (NDGA) or Asn Asp Gln Gly (NDEG) ; n = six or seven units) tetrapeptide units. None of the isolates had an identical sequence at nucleotide level. These findings suggest that polymorphism in CSP is essentially limited to the tandem repeat domain. (Résumé d'auteur)

Sulfadoxine-pyrimethamine is one of the alternative antimalarial drugs used to treat chloroquine-resistant #Plasmodium falciparum$ malaria. The molecular target of sulfadoxine, an analog of p-aminobenzoic acid that inhibits the folate biosynthetic pathway, is dihydropteroate synthase (DHPS). The nucleotide sequence of the DHPS gene was determined in 32 clinical isolates obtained in Yaounde, Cameroon, and compared with the sequence of reference clones and Cambodian strains of #P. falciparum$. Of the 32 Cameroonian isolates, 31 displayed one of the sulfadoxine-sensitive mutation patterns : Ala-436/Ala-437/Ala-581//Ala-613 (n = 20), Ser-436/Gly-437/Ala-581/Ala-613(n = 6), Ser-436/Ala-437/ala-581/Ala-613 (n = 4), and Ala-436/Gly-437/Ala-581/Ala-613 (n = 1). One isolate had a sulfadoxine-resistant profile characterized by a double mutation : Phe-436/Ala-437/Ala-581/Ser-613. Although the majority of the isolates had a sulfadoxine-sensitive genetic profile, further studies are needed to correlate the mutation patterns and in vitro and in vivo sulfadoxine sensitivity. (Résumé d'auteur)

A modified version of a simplified in vivo test was applied to assess the susceptibility of Plasmodium falciparum to chloroquine among semi-immune febrile children in Kouroussa, Guinea. In 27% of cases, a partial response (RI/RII) to chloroquine was observed; the remainder showed a good response (S/RI). This test is both practical and useful to assess the efficacy of chloroquine at the intermediate level of health care services.