Implementation of a Community-Based Hybrid HIV Testing Services Program as a Strategy to Saturate Testing Coverage in Western Kenya.

BACKGROUND: Knowledge of HIV status is the entry point for linkage to prevention, care, and treatment, and the first step toward achieving the UNAIDS 90-90-90 targets. Most countries rely on proxies for estimating testing saturation, including periodic population-based sampling and yield (number positive among those tested). We conducted a community-based "Hybrid" HIV testing services (HTS) program to identify persons unaware of their HIV-positive status. SETTING: Homa Bay County, Kenya; July-September, 2016. METHODS: We conducted community mapping, household census, multi-disease community health campaigns (CHCs), and home-based tracking. HIV testing eligibility was based on 2015 national guidelines. The previously unidentified fraction (PUF) was defined as the proportion of newly identified persons living with HIV (PLWH) out of all previously identified and newly identified PLWH. RESULTS: The Hybrid HTS program reached 28,885 persons in total: 25,340 residents and 3545 nonresidents. There were 19,288 persons reached through CHCs and tracking. Of 11,316 individuals eligible for HIV testing, 9463 (83%) accepted testing, including 1230 (13%) first-time testers. There were 115 newly identified PLWH of 1589 total HIV-positive persons, representing a 7.2% PUF. Of 93 newly identified PLWH at the CHCs, 68% initiated same-day antiretroviral therapy. CONCLUSION: The Hybrid HTS program identified persons previously unaware of their HIV-positive status, thereby enabling linkage to care and same-day treatment and reducing onward transmission risk. An approach focused on identifying persons unaware of their HIV-positive status in combination with ascertaining the PUF has the potential to better target testing strategies to identify >90% of PLWH in a community.

Family-Four Aldehyde Dehydrogenases Play an Indispensable Role in the Pathogenesis of Magnaporthe oryzae.

The oxidative degradation of lipids through lipid peroxidation processes results in the generation of free fatty acid radicals. These free radicals including reactive oxygen species (ROS) serve as a substrate for generating reactive aldehydes. The accumulation of free fatty acid radicals, ROS, and reactive aldehydes in cell compartments beyond physiological threshold levels tends to exert a damaging effect on proximal membranes and distal tissues. Living organisms deploy a wide array of efficient enzymes including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and aldehyde dehydrogenases (ALDHs) for scavenging reactive molecules and intermediates produced from membrane lipid peroxidation events. Although the contributions of SOD, CAT, and POD to the pathogenesis of microbial plant pathogens are well known, the influence of ALDH genes on the morphological and infectious development of plant pathogenic microbes is not well understood. In this study, we deployed RNA interference (RNAi) techniques and successfully silenced two putative family-four aldehyde dehydrogenase genes potassium-activated aldehyde dehydrogenase (MoKDCDH) and delta-1-pyrrorine-5-carboxylate dehydrogenase (MoP5CDH) in the rice blast pathogen Magnaporthe oryzae. The results obtained from the phenotypic analysis of individual knock-down strains showed that the RNAi-mediated inactivation of MoKDCDH and MoP5CDH triggered a significant reduction in conidiogenesis and vegetative growth of ΔMokdcdh and ΔMop5cdh strains. We further observed that downregulating the expression of MoKDCDH and MoP5CDH severely compromised the pathogenesis of the rice blast fungus. Also, the disruption of MoKDCDH and MoP5CDH M. oryzae undermined membrane integrity and rendered the mutant strains highly sensitive to membrane stress inducing osmolytes. However, the MoKDCDH and MoP5CDH knock-down strains generated in this study displayed unaltered cell wall integrity and thus suggested that family-four ALDHs play a dispensable role in enforcing cell wall-directed stress tolerance in M. oryzae. From these results, we deduced that family-four ALDHs play a conserved role in fostering membrane integrity in M. oryzae possibly by scavenging reactive aldehydes, fatty acid radicals, and other alcohol derivatives. The observation that downregulating the expression activities of MoKDCDH had a lethal effect on potential mutants further emphasized the need for comprehensive and holistic evaluation of the numerous ALDHs amassed by the rice blast fungus for their possible engagement as suitable targets as antiblast agents.