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emerging infectious diseases - Top 30 Publications

Current and emerging two-drug approaches for HIV-1 therapy in ART-naïve and ART-experienced, virologically suppressed patients.

Current guidelines recommend a 2-drug antiretroviral regimen as an alternative to triple antiretroviral therapy (ART) in selected patients to reduce long-term toxicity and costs. Areas covered: This review is intended to provide insight into the efficacy, safety and tolerability of 2-drug versus 3-drug ART in naïve and in treatment-experienced virologically-suppressed patients. Expert opinion: Dual therapy regimens are not feasible in HBV-coinfected individuals and should not be applied during pregnancy. Positive data on 2-drug ART in drug naïve patients are still limited, while, in virologically-suppressed individuals, several regimens have shown non-inferiority as compared to 3-drug regimens. The strongest evidence of efficacy applies to ritonavir-boosted PI regimens combined with lamivudine and to dolutegravir with rilpivirine. Dual therapies showed improved renal function and bone mineral density over tenofovir disoproxil fumarate-based 3-drug regimens. There are also great expectations for ongoing phase 3 trials testing dolutegravir with lamivudine. New and future single tablet co-formulations of dual regimens are expected to improve their suitability. Despite the lack of comparison with tenofovir alafenamide-based 3-drug regimens, the 2-drug regimens showing consistent non-inferiority and safety versus 3-drug regimens will challenge the current paradigm of 3-drug ART.

Water treatment and handwashing practices in rural Kenyan health care facilities and households six years after the installation of portable water stations and hygiene training.

Many health care facilities (HCFs) and households in low-and-middle-income countries have inadequate access to water for hygiene and consumption. To address these problems, handwashing and drinking water stations were installed in 53 HCFs with prevention-of-mother-to-child-transmission of HIV programs in Kenya in 2005, and hygiene education was provided to health workers and clinic clients. To assess this program, we selected a random sample of 30 HCFs, observed the percentage of handwashing and drinking water stations that were functional and in use, and after that interviewed health providers and clients about hygiene and water treatment. Results indicated that, six years after implementation, 80.0% of HCFs had at least one functional handwashing station and 83.3% had at least one functional drinking water station. In addition, 60% of HCFs had soap at ≥ one handwashing stations, and 23.3% had ≥ one container with detectable free chlorine. Of 299 clients (mothers with ≥ one child under five), 57.2% demonstrated proper water treatment knowledge, 93.3% reported ever using water treatment products, 16.4% had detectable chlorine residual in stored water, and 89.0% demonstrated proper handwashing technique. Six years after program implementation, although most HCFs had water stations and most clients could demonstrate proper handwashing technique, water stored in most clinics and homes was not treated.

Author Correction: Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis.

In the version of this article initially published, the URL listed for TubercuList was incorrect. The correct URL is https://mycobrowser.epfl.ch/. The error has been corrected in the HTML and PDF versions of the article.

The Plasmodium knowlesi MAHRP2 ortholog localizes to structures connecting Sinton Mulligan's clefts in the infected erythrocyte.

During development within the host erythrocyte malaria parasites generate nascent membranous structures which serve as a pathway for parasite protein transport to modify the host cell. The molecular basis of such membranous structures is not well understood, particularly for malaria parasites other than Plasmodium falciparum. To characterize the structural basis of protein trafficking in the Plasmodium knowlesi-infected erythrocyte, we identified a P. knowlesi ortholog of MAHRP2, a marker of the tether structure that connects membranous structures in the P. falciparum-infected erythrocyte. We show that PkMAHRP2 localizes on amorphous structures that connect Sinton Mulligan's clefts (SMC) to each other and to the erythrocyte membrane. Three dimensional reconstruction of the P. knowlesi-infected erythrocyte revealed that the SMC is a plate-like structure with swollen ends, reminiscent of the morphology of the Golgi apparatus. The PkMAHRP2-localized amorphous structures are possibly functionally equivalent to P. falciparum tether structure. These findings suggest a conservation in the ultrastructure of protein trafficking between P. falciparum and P. knowlesi.

A Novel Fibroblast Growth Factor 15 Dependent- and Bile Acid Independent-Promotion of Liver Regeneration in Mice.

The role of intestine-derived factors in promoting liver regeneration after partial hepatectomy (PHx) are not entirely known, but bile acids (BAs) and fibroblast growth factor 15 (Fgf15) that is highly expressed in the mouse ileum could promote hepatocyte proliferation. Fgf15 strongly suppresses the synthesis of BAs and emerging evidence indicates that Fgf15 is important for liver regeneration. The mechanisms by which Fgf15 promotes liver regeneration are unclear, but Fgf15 may do so indirectly by reducing BA levels and/or directly by promoting cell proliferation. However, it's undetermined whether these two mechanisms are independent or integrated. In this study, we aimed to clarify these relationships by generating novel Fgf15 tet-off, transgenic mice (Fgf15 Tg) that had very low BA levels resulted from overexpressed Fgf15-mediated suppression of BA synthesis. Compared to wild-type mice, the Fgf15 Tg mice showed increased hepatocyte proliferation even without surgery, and a further induction of the genes in cell-cycle progression after PHx. Moreover, overexpression of Fgf15 by AAV-Fgf15 transduction or treatment with the recombinant Fgf15 protein led to increased cell proliferation in vivo. Furthermore, Fgf15 Tg mice exhibited an earlier and greater activation of MAPK, Stat3, and NF-κB signaling pathways in the priming stage, and a disruption of the hippo signaling pathway in the termination stage of liver regeneration.

Longitudinal study of cellular and systemic cytokines signatures define the dynamics of a balanced immune environment in disease manifestation in Zika virus-infected patients.

The unexpected re-emergence of Zika virus (ZIKV) has caused numerous outbreaks globally. This study characterized the host immune responses during ZIKV infection.

Vector competence of Italian Aedes albopictus populations for the chikungunya virus (E1-226V).

Chikungunya virus (CHIKV) is an emerging arbovirus, belonging to the Togaviridae family, Alphavirus genus, transmitted by Aedes spp. mosquitoes. Since 2007, two different CHIKV stains (E1-226A and E1-226V) have been responsible for outbreaks in European countries, including Italy, sustained by Ae. albopictus mosquitoes.

Rodent-borne diseases and their public health importance in Iran.

Rodents are reservoirs and hosts for several zoonotic diseases such as plague, leptospirosis, and leishmaniasis. Rapid development of industry and agriculture, as well as climate change throughout the globe, has led to change or increase in occurrence of rodent-borne diseases. Considering the distribution of rodents throughout Iran, the aim of this review is to assess the risk of rodent-borne diseases in Iran.

The neurological complications of chikungunya virus: A systematic review.

We performed a systematic review on the neurological complications of chikungunya virus. Such complications are being reported increasingly, owing primarily to the scale of recent epidemics but also to a growing understanding of the virus' neurovirulence. We performed a thorough literature search using PubMed and Scopus databases, summating the data on all published reports of neurological disease associated with chikungunya virus. We appraised the data for each major condition in adults, children, and neonates, as well as evaluating the latest evidence on disease pathogenesis and management strategies. The review provides a comprehensive summary for clinicians, public health officials, and researchers tackling the challenges associated with this important emerging pathogen.

Clinical infection in house rats (Rattus rattus) caused by Streptobacillus notomytis.

Rat bite fever is an under-reported, under-diagnosed emerging zoonosis with worldwide distribution. Besides Spirillum minus, Streptobacillus moniliformis is the major causative microorganism although it usually colonises rats without any clinical signs. A group of house rats (Rattus rattus) kept in a zoo exhibition for educational purposes suffered from neurological signs including disorientation, torticollis, stall walking, ataxia and death. Gross pathological and histo-pathological examinations of the investigated rats revealed high-grade otitis interna et media, from which Streptobacillus notomytis was isolated in pure culture or as the predominant microorganism. This case series underlines a previously expressed hypothesis that R. rattus might be naturally colonised with S. notomytis, whereas the traditional rat bite fever organism, S. moniliformis, might be restricted to the Norway rat (Rattus norvegicus). However, the general paucity of Streptobacillus isolates, especially from their respective animal hosts, precludes definitive proof of these host tropisms. This is the first report of S. notomytis detection outside Asia and Australia and the first evidence for its role as a facultative pathogen in house rats.

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