The in vitro activity of artemether against 56 African isolates of Plasmodium falciparum from Senegal was evaluated using an isotope-based drug susceptibility semi-microtest. The 50% inhibitory concentration (IC 50) values for artemether were in a narrow range from 0.8 to 15.2 nM (mean IC 50 3.43 nM) and the 95% confidence interval (CI) was 2.50-4.36 nM. Artemether was equally effective on chloroquine-sensitive and chloroquine-resistant isolates (mean IC 50 346 nM, 95% CI 2.08-4.84 nM versus mean IC 50 2.80 nM, 95% CI 2.00-3.60 nM). There was a significant positive correlation between responses to artemether and mefloquine (r 2 0.36, P 0.001), artemether and quinine (r 2 0.085, P 0.05), artemether and halofantrine (r 2 0.075, P 0.05), quinine and mefloquine (r 2 0.205, P 0.01), quinine and halofantrine (r 2 0.124, P 0.05), and mefloquine and halofantrine (r 2 0.801, P 0.001). A positive correlation between these drugs suggests in vitro cross-resistance or at least in vitro cross-susceptibility. In the absence of effective and practical preventive measures , the only current options for reducing the morbidity and mortality of malaria especially in Africa are chemopro-phylaxis and chemotherapy. For this reason, the increasing prevalence of strains of Plasmodium falciparum resistant to chloroquine and other antimalarial drugs poses a serious problem for control of malaria. 1 There is an urgent need to find and develop alternative drugs against chloroquine-resistant P. falciparum. One group of alternative antimalarial drugs comprises ar-temisinin (qinghaosu) and its derivatives. Artemisinin is a traditional Chinese medicinal herb derived from Artemisia annua. It has a sesquiterpene lactone with a peroxide bridge and antimalarial activity has been attributed to the peroxide moiety 2 by a mechanism involving production of free radicals that damage the parasite membrane. 3 Artemether (an oil-soluble artemisinin derivative) has shown effectiveness against chloroquine-resistant strains of P. falciparum in China and Thailand. 4, 5 However, little information is available concerning the in vitro activity of artemisinin and its derivatives against isolates of P. falciparum from Africa other than reference strains. 6, 7 The twofold aim of this in vitro study was to evaluate the activity of artemether against fresh isolates of P. falcip-arum from Senegal, and to analyze cross-susceptibility between artemether, chloroquine, quinine, mefloquine, and hal-ofantrine. MATERIALS AND METHODS Isolates of P. falciparum. All programs were reviewed and approved by the Conseil de Perfectionnement of the Institut de Dakar, which is presided over by the Senegalese Health Secretary. Informed oral consent was obtained from the patients and/or their parents before collection of blood samples. Only oral consent was obtained because only 5% of the people in Dielmo, Ndiop, and Toubakouta can read and write. Between October 1995 and January 1996, 56 fresh P. falciparum isolates were prepared from samples obtained after oral consent in Diel-mo, Ndi...

The 50% inhibitory concentration (IC 50 s) of benflumetol (range, 12.5 to 240 nM; mean, 55.1 nM) for 158 Senegalese isolates were evaluated. Ten isolates (6%) showed decreased susceptibility to benflumetol. Benflumetol was slightly more potent against chloroquine-resistant isolates (P < 0.025). No correlation or weak correlations in the responses to benflumetol and pyrimethamine, chloroquine, amodiaquine, artemether, quinine, and pyronaridine were observed, and these correlations are insufficient to suggest cross-resistance. Benflumetol may be an important alternative drug for the treatment of chloroquine-resistant malaria.

DNA markers used for individual identification in forensic sciences are based on repeat sequences in nuclear DNA and the mitochondrial DNA hypervariable regions 1 and 2. An alternative to these markers is the use of single nucleotide polymorphisms (SNPs). These have a particular advantage in the analysis of degraded or poor samples, which are often all that is available in forensics or anthropology. In order to study the potential of SNP analysis in these fields, 41 SNPs were selected on the basis of following criteria: conservation, lack of phenotypic expression, and frequency of occurrence in populations. Thirty-six autosomal SNPs were used for genotyping 21 inclusionary and 3 exclusionary paternity cases. The behavior of 5 X-chromosome SNPs was analyzed in a French representative population. Our approach to SNP typing is a multiplex PCR based amplification followed by simultaneous detection by primer extension (PEX) analyzed by Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). The selected autosomal SNPs showed independent inheritance and gave clear results in paternity investigation. All X-SNPs were useful as both paternity and identification markers. PEX and MALDI-TOF MS, with their high sensitivity, precision and speed, gave a powerful method for forensic and anthropological exploitation of biallelic markers.

In cases of stains that contain mixed DNA from different contributors, analyzing mitochondrial DNA (mtDNA) requires the use of cloning techniques. We developed an efficient cloning technique that was applied in a rape case. After a differential lysis-based DNA extraction from vaginal swabs, hypervariable region I and II (HVI, HVII) amplicons obtained from the male fraction were cloned. Although we mainly found the victim's haplotype, we were able to detect the suspect's haplotype in two clones for HVI and in one clone for HVII. As the midpiece of the flagellum, which contains mitochondria, can be lost during the differential lysis, we also investigated the female fraction by cloning to evaluate the proportion of victim/suspect mtDNA. Unfortunately, only clones presenting the victim's haplotype were found. This case highlights the need for an optimal differential lysis protocol to enrich the male fraction not only with nuclear but also mitochondrial DNA.

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X-chromosomal short tandem repeats (X-STRs) are very useful in complex paternity cases because they are inherited by male and female offspring in different ways. They complement autosomal STRs (as-STRs) allowing higher paternity probabilities to be attained. These probabilities are expressed in a likelihood ratio (LR). The formulae needed to calculate LR depend on the genotype combinations of suspected pedigrees. LR can also be obtained by the use of Bayesian networks (BNs). These are graphical representations of real situations that can be used to easily calculate complex probabilities. In the present work, two BNs are presented, which are designed to derive LRs for half-sisters/half-sisters and mother/daughter/paternal grandmother relationships. These networks were validated against known formulae and show themselves to be useful in other suspect pedigree situations than those for which they were developed. The BNs were applied in two paternity cases. The application of the mother/daughter/paternal grandmother BN highlighted the complementary value of X-STRs to as-STRs. The same case evaluated without the mother underlined that missing information tends to be conservative if the alleged father is the biological father and otherwise nonconservative. The half-sisters case shows a limitation of statistical interpretations in regard to high allelic frequencies.

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