The delivery of safe and effective radical cure for Plasmodium vivax is one of the greatest challenges for achieving malaria elimination from the Asia–Pacific by 2030. During the annual meeting of the Asia Pacific Malaria Elimination Network Vivax Working Group in October 2016, a round table discussion was held to discuss the programmatic issues hindering the widespread use of primaquine (PQ) radical cure. Participants included 73 representatives from 16 partner countries and 33 institutional partners and other research institutes. In this meeting report, the key discussion points are presented and grouped into five themes: (i) current barriers for glucose-6-phosphate deficiency (G6PD) testing prior to PQ radical cure, (ii) necessary properties of G6PD tests for wide scale deployment, (iii) the promotion of G6PD testing, (iv) improving adherence to PQ regimens and (v) the challenges for future tafenoquine (TQ) roll out. Robust point of care (PoC) G6PD tests are needed, which are suitable and cost-effective for clinical settings with limited infrastructure. An affordable and competitive test price is needed, accompanied by sustainable funding for the product with appropriate training of healthcare staff, and robust quality control and assurance processes. In the absence of quantitative PoC G6PD tests, G6PD status can be gauged with qualitative diagnostics, however none of the available tests is currently sensitive enough to guide TQ treatment. TQ introduction will require overcoming additional challenges including the management of severely and intermediately G6PD deficient individuals. Robust strategies are needed to ensure that effective treatment practices can be deployed widely, and these should ensure that the caveats are outweighed by the benefits of radical cure for both the patients and the community. Widespread access to quality controlled G6PD testing will be critical.
Heterochromatin-associated gene silencing controls multiple physiological processes in malaria parasites, however, little is known concerning the regulatory network and cis-acting sequences involved in the organization of heterochromatin and how they modulate heterochromatic gene expression. Based on systematic profiling of genome-wide occupancy of eighteen Apicomplexan AP2 transcription factors by ChIP-seq analysis, we identify and characterize eight heterochromatin-associated factors (PfAP2-HFs), which exhibit preferential enrichment within heterochromatic regions but with differential coverage profiles. Although these ApiAP2s target euchromatic gene loci via specific DNA motifs, they are likely integral components of heterochromatin independent of DNA motif recognition. Systematic knockout screenings of ApiAP2 factors coupled with RNA-seq transcriptomic profiling revealed three activators and three repressors of heterochromatic gene expression including four PfAP2-HFs. Notably, expression of virulence genes is either completely silenced or significantly reduced upon the depletion of PfAP2-HC. Integrated multi-omics analyses reveal autoregulation and feed-forward loops to be common features of the ApiAP2 regulatory network, in addition to the occurrence of dynamic interplay between local chromatin structure and ApiAP2s in transcriptional control. Collectively, this study provides a valuable resource describing the genome-wide landscape of the ApiAP2 family and insights into functional divergence and cooperation within this family during the blood-stage development of malaria parasites.
An emigrant worker returning from Southeast Asia triggered the outbreak of a DF epidemic in Zhejiang province, China, in October, 2004. Eighty-three cases, mainly young and middle-aged people between 20 and 50 (78.3%), were reported in the area of Cixi. There were no obvious occupational patterns. The majority of cases were female, with a sex ratio of 1:1.86 (m:f). The dengue virus (DENV) strains from the epidemic area were isolated and identified as DENV-1, which belongs to Asian strain 1. According to the epidemiological investigation, the incidence of DF had no relationship to temperature, humidity, or precipitation, and the Breteau index of larvae showed a clear relationship only with the House Index and Container Index. Recent dengue problems in the town have been associated with the complex social factors and hygienic conditions for endemic villagers and immigrant workers. Some hygienic measures should be taken by the local government to reduce the risk of mosquito-borne disease. These measures should aim to eliminate the breeding sites of the vector Aedes albopictus in indoor and outdoor containers filled with rainwater and thus reducing the risk of DF transmission.
It is known that selective sacral roots rhizotomy is effective for relieving the neurogenic bladder associated with spinal cord injury. The goal of this study is to review the surgical anatomy of the lumbosacral nerve rootlets and to provide some morphological bases for highly selective sacral roots rhizotomy. Spinal cord dissections were performed on five cadavers under surgical microscope. At each spinal cord segment, we recorded the number, diameter and length of the rootlets, subbundles and bundles from the L1 to S2 spinal segments, and the length of the dorsal/ventral root entry zone. Peripheral nervous system myelin was examined by immunohistochemistry. We found: (1) the ventral or the dorsal root of the lumbosacral segment of the spinal cord was divided into one to three nerve bundles and each bundle was subdivided into one to three subbundles. Each subbundle further gave out two to three rootlets connected with the spinal cord; (2) there were no significant differences in the number of rootlets within the L1 to S2 segments, but the size of rootlets and the length of nerve roots varied (P < 0.05); and (3) the more myelinated fibers a rootlet contained, the larger transection area it had. The area of peripheral nervous system myelin positive cells and the total area of rootlets were correlated (P < 0.001). Thus, during highly selective sacral roots rhizotomy, the ventral and dorsal roots can be divided into several bundles of rootlets, and we could initially distinct the rootlets by their diameters. Anat Rec, 293:2123Rec, 293: -2128Rec, 293: , 2010. V V C 2010 Wiley-Liss, Inc.Key words: microsurgical anatomy; lumbosacral nerve rootlet; highly selective sacral rootlets rhizotomy; spinal cord injuryInjuries to the central nervous system in humans are associated with a low degree of neurological recovery and, in most cases, lifelong debilitation. Spinal cord injury (SCI) can result not only in paraplegia or quadriplegia but also in loss of urinary and defecatory control as well as alteration of sexual function (Pedersen, 1983;
An emigrant worker returning from Southeast Asia triggered the outbreak of a DF epidemic in Zhejiang province, China, in October, 2004. Eighty-three cases, mainly young and middle-aged people between 20 and 50 (78.3%), were reported in the area of Cixi. There were no obvious occupational patterns. The majority of cases were female, with a sex ratio of 1:1.86 (m:f). The dengue virus (DENV) strains from the epidemic area were isolated and identified as DENV-1, which belongs to Asian strain 1. According to the epidemiological investigation, the incidence of DF had no relationship to temperature, humidity, or precipitation, and the Breteau index of larvae showed a clear relationship only with the House Index and Container Index. Recent dengue problems in the town have been associated with the complex social factors and hygienic conditions for endemic villagers and immigrant workers. Some hygienic measures should be taken by the local government to reduce the risk of mosquito-borne disease. These measures should aim to eliminate the breeding sites of the vector Aedes albopictus in indoor and outdoor containers filled with rainwater and thus reducing the risk of DF transmission.
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