Modelling the impact of CD4 testing on mortality from TB and cryptococcal meningitis among patients with advanced HIV disease in nine countries.

INTRODUCTION: Despite antiretroviral therapy (ART) scale-up among people living with HIV (PLHIV), those with advanced HIV disease (AHD) (defined in adults as CD4 count <200 cells/mm3 or clinical stage 3 or 4), remain at high risk of death from opportunistic infections. The shift from routine baseline CD4 testing towards viral load testing in conjunction with "Test and Treat" has limited AHD identification. METHODS: We used official estimates and existing epidemiological data to project deaths from tuberculosis (TB) and cryptococcal meningitis (CM) among PLHIV-initiating ART with CD4 <200 cells/mm3 , in the absence of select World Health Organization recommended diagnostic or therapeutic protocols for patients with AHD. We modelled the reduction in deaths, based on the performance of screening/diagnostic testing and the coverage and efficacy of treatment/preventive therapies for TB and CM. We compared projected TB and CM deaths in the first year of ART from 2019 to 2024, with and without CD4 testing. The analysis was performed for nine countries: South Africa, Kenya, Lesotho, Mozambique, Nigeria, Uganda, Zambia, Zimbabwe and the Democratic Republic of Congo. RESULTS: The effect of CD4 testing comes through increased identification of AHD and consequent eligibility for protocols for AHD prevention, diagnosis and management; algorithms for CD4 testing avert between 31% and 38% of deaths from TB and CM in the first year of ART. The number of CD4 tests required per death averted varies widely by country from approximately 101 for South Africa to 917 for Kenya. CONCLUSIONS: This analysis supports retaining baseline CD4 testing to avert deaths from TB and CM, the two most deadly opportunistic infections among patients with AHD. However, national programmes will need to weigh the cost of increasing CD4 access against other HIV-related priorities and allocate resources accordingly.

Cost-effectiveness of voluntary medical male circumcision for HIV prevention across sub-Saharan Africa: results from five independent models.

BACKGROUND: Voluntary medical male circumcision (VMMC) has been a recommended HIV prevention strategy in sub-Saharan Africa since 2007, particularly in countries with high HIV prevalence. However, given the scale-up of antiretroviral therapy programmes, it is not clear whether VMMC still represents a cost-effective use of scarce HIV programme resources. METHODS: Using five existing well described HIV mathematical models, we compared continuation of VMMC for 5 years in men aged 15 years and older to no further VMMC in South Africa, Malawi, and Zimbabwe and across a range of setting scenarios in sub-Saharan Africa. Outputs were based on a 50-year time horizon, VMMC cost was assumed to be US$90, and a cost-effectiveness threshold of US$500 was used. FINDINGS: In South Africa and Malawi, the continuation of VMMC for 5 years resulted in cost savings and health benefits (infections and disability-adjusted life-years averted) according to all models. Of the two models modelling Zimbabwe, the continuation of VMMC for 5 years resulted in cost savings and health benefits by one model but was not as cost-effective according to the other model. Continuation of VMMC was cost-effective in 68% of setting scenarios across sub-Saharan Africa. VMMC was more likely to be cost-effective in modelled settings with higher HIV incidence; VMMC was cost-effective in 62% of settings with HIV incidence of less than 0·1 per 100 person-years in men aged 15-49 years, increasing to 95% with HIV incidence greater than 1·0 per 100 person-years. INTERPRETATION: VMMC remains a cost-effective, often cost-saving, prevention intervention in sub-Saharan Africa for at least the next 5 years. FUNDING: Bill & Melinda Gates Foundation for the HIV Modelling Consortium.

Early Cambrian renewal of the geodynamo and the origin of inner core structure.

Paleomagnetism can elucidate the origin of inner core structure by establishing when crystallization started. The salient signal is an ultralow field strength, associated with waning thermal energy to power the geodynamo from core-mantle heat flux, followed by a sharp intensity increase as new thermal and compositional sources of buoyancy become available once inner core nucleation (ICN) commences. Ultralow fields have been reported from Ediacaran (~565 Ma) rocks, but the transition to stronger strengths has been unclear. Herein, we present single crystal paleointensity results from early Cambrian (~532 Ma) anorthosites of Oklahoma. These yield a time-averaged dipole moment 5 times greater than that of the Ediacaran Period. This rapid renewal of the field, together with data defining ultralow strengths, constrains ICN to ~550 Ma. Thermal modeling using this onset age suggests the inner core had grown to 50% of its current radius, where seismic anisotropy changes, by ~450 Ma. We propose the seismic anisotropy of the outermost inner core reflects development of a global spherical harmonic degree-2 deep mantle structure at this time that has persisted to the present day. The imprint of an older degree-1 pattern is preserved in the innermost inner core.

Engagement in local and collaborative wildfire risk mitigation planning across the western U.S.-Evaluating participation and diversity in Community Wildfire Protection Plans.

Since their introduction two decades ago, Community Wildfire Protection Plans (CWPPs) have become a common planning tool for improving community preparedness and risk mitigation in fire-prone regions, and for strengthening coordination among federal and state land management agencies, local government, and residents. While CWPPs have been the focus of case studies, there are limited large-scale studies to understand the extent of, and factors responsible for, variation in stakeholder participation-a core element of the CWPP model. This article describes the scale and scope of participation in CWPPs across the western United States. We provide a detailed account of participants in over 1,000 CWPPs in 11 states and examine how levels of participation and stakeholder diversity vary as a function of factors related to planning process, planning context, and the broader geographic context in which plans were developed. We find that CWPPs vary substantially both by count and diversity of participants and that the former varies as a function of the geographic scale of the plan, while the latter varies largely as a function of the diversity of landowners within the jurisdiction. More than half of participants represented local interests, indicating a high degree of local engagement in hazard mitigation. Surprisingly, plan participation and diversity were unrelated to wildfire hazard. These findings suggest that CWPPs have been largely successful in their intent to engage diverse stakeholders in preparing for and mitigating wildfire risk, but that important challenges remain. We discuss the implications of this work and examine how the planning process and context for CWPPs may be changing.

The voluntary medical male circumcision Site Capacity and Productivity Assessment Tool (SCPT): An innovative visual management tool to optimize site service delivery.

Given constrained funding for HIV, achieving global goals on VMMC scale-up requires that providers improve service delivery operations and use labor and capital inputs as efficiently as possible to produce as many quality VMMCs as feasible. The Voluntary Medical Male Circumcision Site Capacity and Productivity Assessment Tool (SCPT) is an electronic visual management tool developed to help VMMC service providers to understand and improve their site's performance. The SCPT allows VMMC providers to: 1) track the most important human resources and capital inputs to VMMC service delivery, 2) strategically plan site capacity and targets, and 3) monitor key site-level VMMC service delivery performance indicators. To illustrate a real-world application of the SCPT, we present selected data from two provinces in Mozambique-Manica and Tete, where the SCPT was piloted We looked at the data prior to the introduction of SCPT (October 2014 to August 2016), and during the period when the tool began to be utilized (September 2016 to September 2017). The tool was implemented as part of a broader VMMC site optimization strategy that VMMC implementers in Mozambique put in place to maximize programmatic impact. Routine program data for Manica and Tete from October 2014 to September 2017 showcase the turnaround of the VMMC program that accompanied the implementation of the SCPT together with the other components of the VMMC site optimizatio strategy. From October 2016, there was a dramatic increase in the number of VMMCs performed. The number of fixed service delivery sites providing VMMC services was expanded, and each fixed site extended service delivery by performing VMMCs in outreach sites. Alignment between site targets and the number of VMMCs performed improved from October 2016. Utilization rates stabilized between October 2016 and September 2017, with VMMCs performed closely tracking VMMC site capacity in most sites. The SCPT is designed to address the need for site level data for programmatic decision-making during site planning, implementation, monitoring and evaluation. Deployment of the SCPT can help VMMC providers monitor the performance of VMMC service delivery sites and improve their performance. We recommend use of the customized version of this tool and model to the need of other programs.