Plasmodium falciparum: Differential Selection of Drug Resistance Alleles in Contiguous Urban and Peri-Urban Areas of Brazzaville, Republic of Congo

The African continent is currently experiencing rapid population growth, with rising urbanization increasing the percentage of the population living in large towns and cities. We studied the impact of the degree of urbanization on the population genetics of Plasmodium falciparum in urban and peri-urban areas in and around the city of Brazzaville, Republic of Congo. This field setting, which incorporates local health centers situated in areas of varying urbanization, is of interest as it allows the characterization of malaria parasites from areas where the human, parasite, and mosquito populations are shared, but where differences in the degree of urbanization (leading to dramatic differences in transmission intensity) cause the pattern of malaria transmission to differ greatly. We have investigated how these differences in transmission intensity affect parasite genetic diversity, including the amount of genetic polymorphism in each area, the degree of linkage disequilibrium within the populations, and the prevalence and frequency of drug resistance markers. To determine parasite population structure, heterozygosity and linkage disequilibrium, we typed eight microsatellite markers and performed haplotype analysis of the msp1 gene by PCR. Mutations known to be associated with resistance to the antimalarial drugs chloroquine and pyrimethamine were determined by sequencing the relevant portions of the crt and dhfr genes, respectively. We found that parasite genetic diversity was comparable between the two sites, with high levels of polymorphism being maintained in both areas despite dramatic differences in transmission intensity. Crucially, we found that the frequencies of genetic markers of drug resistance against pyrimethamine and chloroquine differed significantly between the sites, indicative of differing selection pressures in the two areas

Effetti dell'allenamento isocinetico sulla risposta cardiocircolatoria del soggetto anziano

The maximal oxygen uptake (VO 2max) is commonly used for assessing the individual aerobic fitness. Many studies have shown in elderly subjects that an increase in cardiorespiratory function and VO 2max can be achieved with endurance training, but the effects of strength conditioning on cardiovascular fitness and aerobic power have not been extensively examined in older subjects. The lack of data concerning the effects of isokinetic training on cardiopulmonary function in elderly subjects has prompted the present study. Eight sedentary men (average 68 \ub1 4 years) underwent 13 weeks of isokinetic training, two sessions per week lasting one hour each. One week before and two-three days after the training period each subject performed: A) isokinetic strength test evaluating the knee extensor and flexor muscles; B) incremental exercise on a bicycle ergometer up to voluntary exhaustion. In addition, measurement of quadriceps cross-sectional area (CSA) was carried out by means of nuclear magnetic resonance imaging. At all investigated angular velocities there was, after training, a significant (p < 0.05) increase of both extensor and flexor muscles isokinetic strength. After training all investigated subjects showed during exercise B) lower values of heart rate (HR) both at rest and at the same absolute workload. The average value of maximal oxygen consumption (VO 2 peak) increased from 24.9 to 27.6 ml\ub7min -1\ub7kg -1 (p < 0.01). A linear relationship (p < 0.05) was found between VO 2 peak and CSA values obtained both before and after training. The results of the present study have shown that, at least in our limited group of sedentary elderly men, isokinetic strength training program besides improve muscle mass and strenght may also increase maximal aerobic power. Furthermore this latter resulted close correlated with the quadriceps CSA value, supporting a causal role for peripheral factors in determining VO 2 peak. From these findings it appears beneficial for elderly population to add to traditional aerobic rehabilitation/training protocols, a series of isokinetic exercises

Effetti dell&apos;allenamento isocinetico sulla risposta cardiocircolatoria del soggetto anziano

The maximal oxygen uptake (VO 2max) is commonly used for assessing the individual aerobic fitness. Many studies have shown in elderly subjects that an increase in cardiorespiratory function and VO 2max can be achieved with endurance training, but the effects of strength conditioning on cardiovascular fitness and aerobic power have not been extensively examined in older subjects. The lack of data concerning the effects of isokinetic training on cardiopulmonary function in elderly subjects has prompted the present study. Eight sedentary men (average 68 \ub1 4 years) underwent 13 weeks of isokinetic training, two sessions per week lasting one hour each. One week before and two-three days after the training period each subject performed: A) isokinetic strength test evaluating the knee extensor and flexor muscles; B) incremental exercise on a bicycle ergometer up to voluntary exhaustion. In addition, measurement of quadriceps cross-sectional area (CSA) was carried out by means of nuclear magnetic resonance imaging. At all investigated angular velocities there was, after training, a significant (p < 0.05) increase of both extensor and flexor muscles isokinetic strength. After training all investigated subjects showed during exercise B) lower values of heart rate (HR) both at rest and at the same absolute workload. The average value of maximal oxygen consumption (VO 2 peak) increased from 24.9 to 27.6 ml\ub7min -1\ub7kg -1 (p < 0.01). A linear relationship (p < 0.05) was found between VO 2 peak and CSA values obtained both before and after training. The results of the present study have shown that, at least in our limited group of sedentary elderly men, isokinetic strength training program besides improve muscle mass and strenght may also increase maximal aerobic power. Furthermore this latter resulted close correlated with the quadriceps CSA value, supporting a causal role for peripheral factors in determining VO 2 peak. From these findings it appears beneficial for elderly population to add to traditional aerobic rehabilitation/training protocols, a series of isokinetic exercises

BK virus sequences in specimens from aborted fetuses

Given the conflicting results of the few published studies, the aim of this retrospective molecular-based study of 10 aborted fetuses that underwent complete autopsy and 10 placentas was carried out to determine whether BK polyomavirus (BKV) can be transmitted transplacentally. The interruption of pregnancy was due to a miscarriage (five cases) or a prenatal diagnosis of severe intrauterine malformations (five cases). Samples from the brain, heart, lung, thymus, liver, and kidney were taken from each fetus, and two samples were obtained from all of the placentas. The presence of BKV was investigated by means of PCR using primers specific for the transcription control region (TCR) and viral capsidic protein 1 (VP1) and DNA extracted from formalin-fixed, paraffin-embedded tissue. BKV genome was detected in 22 of 60 samples (36.6%) from seven fetuses (70%), regardless of the cause of abortion: VP1 was amplified in 12 samples (54%), TCR in seven (32%), and both in three (14%). VP1 was also detected in one placental sample. BKV sequences were most frequently detected in heart and lung (five cases), but sequence analyses of TCR and VP1 revealed a high degree of genomic variability among the samples taken from different organs and the placenta. These results indicate that BKV can cross the placenta during pregnancy and become latent in fetal organs other than the kidney and brain (previously considered the main targets of BKV latency). This may happen in early pregnancy and does not seem to be associated with an increased risk of abortion

Human Genetic Variation Is Associated With Plasmodium falciparum Drug Resistance

One approach to investigate if human genetic variation influences the selection of Plasmodium falciparum drug resistance is to compare the frequency of resistant infections among human populations differing in their genetic background and living in the same epidemiological context. A further complementary approach consists in comparing drug resistance among subjects differing for genes involved in drug metabolism. Here we report, from malariological surveys performed in Burkina Faso, that the prevalence of P. falciparum chloroquine-resistant infections (pfcrt 76T and/or pfmdr1 86Y alleles) differs among sympatric ethnic groups, being higher in the Mossi and Rimaibe groups than in the Fulani group (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.27-3.92; P = .007). The association analysis revealed that the human CYP2C8*2 variant, known to determine a poor drug metabolizer phenotype, was associated with P. falciparum chloroquine-resistant infections (OR, 1.66; 95% CI, 1.13-2.43; P = .008). This variant is more frequent in the Mossi-Rimaibe group (23.7% +/- 1.4%) than in the Fulani group (9.9% +/- 2.5%; P = .0003). This study provides an example of how host genetic variation may influence the selection dynamics of a pathogen's drug resistance