A test of the chromosomal theory of ecotypic speciation in Anopheles gambiae

The role of chromosomal inversions in speciation has long been of interest to evolutionists. Recent quantitative modeling has stimulated reconsideration of previous conceptual models for chromosomal speciation. Anopheles gambiae, the most important vector of human malaria, carries abundant chromosomal inversion polymorphism nonrandomly associated with ecotypes that mate assortatively. Here, we consider the potential role of paracentric inversions in promoting speciation in A. gambiae via "ecotypification," a term that refers to differentiation arising from local adaptation. In particular, we focus on the Bamako form, an ecotype characterized by low inversion polymorphism and fixation of an inversion, 2Rj, that is very rare or absent in all other forms of A. gambiae. The Bamako form has a restricted distribution by the upper Niger River and its tributaries that is associated with a distinctive type of larval habitat, laterite rock pools, hypothesized to be its optimal breeding site. We first present computer simulations to investigate whether the population dynamics of A. gambiae are consistent with chromosomal speciation by ecotypification. The models are parameterized using field observations on the various forms of A. gambiae that exist in Mali, West Africa. We then report on the distribution of larvae of this species collected from rock pools and more characteristic breeding sites nearby. Both the simulations and field observations support the thesis that speciation by ecotypification is occurring, or has occurred, prompting consideration of Bamako as an independent species.     

Efficacy, safety, and selection of molecular markers of drug resistance by two ACTs in Mali

We conducted a randomized single-blinded trial comparing the efficacy and safety of artesunate (AS) + amodiaquine (AQ, 3 days) versus AS (3 days) + sulfadoxine-pyrimethamine (SP, single dose) versus AS monotherapy (5 days) in Southern Mali. Uncomplicated malaria cases were followed for 28 days. Molecular markers of drug resistance were determined. After identification of recrudescences by genotyping, both artemisinin-based combination therapies (ACTs) reached nearly 100% efficacy at Day 14 and Day 28 versus 98.3% and 96.5% for AS, respectively (P > 0.05). AS + SP significantly selected DHFR and DHPS mutations associated with sulfadoxine and pyrimethamine resistance (P < 0.001), and AS + AQ equally selected PfCRT and PfMDR1 point mutations associated with chloroquine and AQ resistance (P < 0.001). No significant adverse event attributable to any of the study drugs was found. The ACTs were efficacious and safe, but the selection of markers for resistance to the partner drugs raises concerns over their lifespan in areas of intense malaria transmission.     

The Impact of Six Annual Rounds of Mass Drug Administration on Wuchereria bancrofti Infections in Humans and in Mosquitoes in Mali

Wuchereria bancrofti prevalence and transmission were assessed in six endemic villages in Sikasso, Mali prior to and yearly during mass drug administration (MDA) with albendazole and ivermectin from 2002 to 2007. Microfilaremia was determined by calibrated thick smear of night blood in adult volunteers and circulating filarial antigen was measured using immunochromatographic card test in children < 5 years of age. Mosquitoes were collected by human landing catch from July to December. None of the 686 subjects tested were microfilaremic 12 months after the sixth MDA round. More importantly, circulating antigen was not detected in any of the 120 children tested, as compared with 53% (103/194) before the institution of MDA. The number of infective bites/human/year decreased from 4.8 in 2002 to 0.04 in 2007, and only one mosquito containing a single infective larva was observed 12 months after the final MDA round. Whether this dramatic reduction in transmission will be sustained following cessation of MDA remains to be seen.     

Repeated artemisinin-based combination therapies in a malaria hyperendemic area of Mali: efficacy, safety, and public health impact

Artemisinin-based combination therapies (ACTs) are the first-line treatment of uncomplicated malaria. The public health benefit and safety of repeated administration of a given ACT are poorly studied. We conducted a randomized trial comparing artemether-lumefantrine, artesunate plus amodiaquine (AS+AQ) and artesunate plus sulfadoxine-pyrimethamine (AS+SP) in patients 6 months of age and older with uncomplicated malaria in Mali from July 2005 to July 2007. The patient received the same initial treatment of each subsequent uncomplicated malaria episode except for treatment failures where quinine was used. Overall, 780 patients were included. Patients in the AS+AQ and AS+SP arms had significantly less risk of having malaria episodes; risk ratio (RR) = 0.84 (P = 0.002) and RR = 0.80 (P = 0.001), respectively. The treatment efficacy was similar and above 95% in all arms. Although all drugs were highly efficacious and well tolerated, AS+AQ and AS+SP were associated with less episodes of malaria.     

A case report of a papillary fibroelastoma arising from the left ventricular outflow septum just beneath the aortic valve

Cardiac papillary fibroelastomas are rare benign tumors with frond-like growths that typically involve the native valve tissue. Papillary fibroelastomas originate less commonly in the ventricular septum. We report a rare case of fibroelastoma arising from the left ventricle.     

下颌骨牵引成骨过程中应变测试动物模型的设计和建立

目的:设计并装配用于下颌骨牵引成骨应变测试的牵引器,建立一种操作简便的下颌骨牵引成骨的应变测试动物模型。方法:自行设计并装配可用于下颌骨牵引成骨过程中应变测试的牵引器,12只大耳白兔下颌角与体部交界处行骨切开术后,用黏固有应变片改制的颌骨牵引器牵引,并比较不同聚氨酯和硅橡胶包封剂,寻找适合的包封剂,牵引完成后,通过大体和X射线观察牵引成骨的情况。结果:动物均完成牵引实验,聚氨酯包封剂组没有完成牵引应变的测试,硅橡胶包封剂组成功完成测试。结论:使用硅橡胶包封的动物模型是理想的牵引成骨应变测试动物模型。     

Iron status in Nigerian mothers and their newborns.

An evaluation of iron status was carried out on 364 Nigerian pregnant women from Niamey at delivery and in cord blood from their newborns. Anemia, defined as a low hematocrit value, was observed in 46% of pregnant women. Iron deficiency, recognized by a combination of, at least, 2 abnormal values in the 3 independent indicators measured (serum ferritin level, erythrocyte protoporphyrin concentration and transferrin saturation) was present in 47.8% of pregnant women. Anemia was associated with iron deficiency in 60.1% of cases in anemic mothers. A correlation between maternal and newborn iron indicators was found. This study points out the necessity for developing strategies in Sahelian countries to combat iron deficiency during pregnancy by specific measures in combination with more general interventions.     

Molecular identification of Wolbachia from the filarial nematode Mansonella perstans

Wolbachiae are bacterial endosymbionts of insects and many filarial nematodes whose products trigger inflammation in filarial infections. The dependence of the parasites on their endosymbionts has also led to the use of antibiotics directed against the Wolbachiae, therapy that has been demonstrated to have a profound salutary effect on filarial infections. The identification of Wolbachiae in Mansonella species has been conclusively shown for Mansonella ozzardi (Mo), but not for Mansonella perstans (Mp). Using primers known to amplify the 16S ribosomal DNA of other filarial Wolbachiae, an identical 1393bp band was found in all samples tested. Sequence analysis of these samples demonstrated a single consensus sequence for Mp Wolbachia 16S rDNA that was most similar to Wolbachia sequences from other filarial nematodes. When aligned with the only other Mansonella Wolbachia sequence (Mo) there were only 8 nucleotide differences in the 1369bp overlapping sequence. Phylogenetic dendrograms, examining the relationship of the Mp Wolbachia to other Wolbachia 16S rDNA, showed that the Wolbachia tracked almost identically to the 5S rRNA of their parasite host. Wolbachia surface protein (WSP) was also demonstrated in protein extracted from Mp-containing whole blood. In advance of a treatment trial of Mp, a method for the quantitation of Mp Wolbachia was developed and used to demonstrate not only a relationship between microfilarial numbers and Wolbachia copy numbers, but also to demonstrate the effect of antibiotic on ridding Mp of Wolbachia.