Pre-exposure Prophylaxis: The Delivery Challenge

HIV pre-exposure prophylaxis (PrEP), despite its efficacy, has been slow in uptake throughout the world. This article discusses the operational and service delivery complexity, based on early real-world experience, with some recommendations on how this promising intervention could be made more available. Currently, access to PrEP is made complex by restricting delivery to dedicated health facilities, as well as requirements around HIV testing and toxicity monitoring. Expanding to verticalized services that focus on well-defined populations where HIV testing and treatment programmes already exist, has proven relatively simple. Providing PrEP outside of this environment has yet to be demonstrated at any scale, and will likely require innovative thinking addressing the regulatory and clinical environment, so as to ensure easier access to this promising HIV prevention tool

Protease Inhibitor Resistance Is Uncommon in HIV-1 Subtype C Infected Patients on Failing Second-Line Lopinavir/r-Containing Antiretroviral Therapy in South Africa

Limited data exist on HIV-1 drug resistance patterns in South Africa following second-line protease-inhibitor containing regimen failure. This study examined drug resistance patterns emerging in 75 HIV-1 infected adults experiencing virologic failure on a second-line regimen containing 2 NRTI and lopinavir/ritonavir. Ninety six percent of patients (n = 72) were infected with HIV-1 subtype C, two patients were infected with HIV-1 subtype D and one with HIV-1 subtype A1. Thirty nine percent (n = 29) of patients had no resistance mutations in protease or reverse transcriptase suggesting that medication non-adherence was a major factor contributing to failure. Major lopinavir resistance mutations were infrequent (5 of 75; 7%), indicating that drug resistance is not the main barrier to future viral suppression

Detection of human papillomavirus DNA with in situ hybridisation in oral squamous carcinoma in a rural black population

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ESTABLISHING A PLATFORM FOR SPRAY DRYING INHALABLE VACCINES IN SOUTH AFRICA

Mycobacterium bovis BCG is the current vaccine for tuberculosis (TB). However, BCG as it is currently administered shows highly variable efficacy in protecting adults against TB. The natural route of infection of TB is via inhalation of bacilli-containing aerosols and it is postulated that immunization by the natural route of infection may lead to a greater immunity given the fact that the lungs are the primary target of infection. By eliciting both local and systemic immune responses, it is anticipated that an inhaled form of BCG will offer greater protection against pulmonary TB. Current commercial BCG vaccine preparations are filled as bacterial suspensions in vials, dried through lyophilization and stabilized through refrigeration with a one year shelf life. However, freeze-dried BCG does not exhibit a particle form conducive for delivery via the aerosol route and must be injected. Spray drying studies by Harvard University and Medicine in Need (MEND) scientists have demonstrated that BCG could be spray dried into a viable aerosol with up to 1 year of stability under refrigerated conditions, with the potential for room temperature stability. To support the further preclinical development of the BCG aerosol for application in the developing world, MEND established a state-of-the-art Biosafety level 3 spray drying facility with local expertise in South Africa, where the vaccine will be produced for an IND-enabling toxicology study meeting OECD Good Laboratory Practice (GLP) requirements. Frozen BCG bulk is spray dried and the resulting dry powder is characterized in terms of viability and aerosol properties. The dried BCG aerosol is then aseptically filled into capsules using a semi-automatic filling device for delivery using a low-cost hand-held inhaler. In conclusion, the spray drying technology was successfully transferred from Harvard University to the MEND facility in Pretoria. MEND is developing local expertise and infrastructure to support further preclinical and clinical development of BCG for inhalation

Intrinsic and extrinsic factors influencing large African herbivore movements

This document is the Accepted Manuscript version of the following article: Jan A. Venter, Herbert H. T. Prins, Alla Mashanova, Willem F. de Boer, and Rob Slotow, 'Intrinsic and extrinsic factors influencing large African herbivore movements', Ecological Informatics, Vol. 30: 257-262, November 2015, doi: https://doi.org/10.1016/j.ecoinf.2015.05.006. This manuscript version is made available under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.Understanding environmental as well as anthropogenic factors that influence large herbivore ecological patterns and processes should underpin their conservation and management. We assessed the influence of intrinsic, extrinsic environmental and extrinsic anthropogenic factors on movement behaviour of eight African large herbivore species. A cumulative odds ordinal logistic regression was used to determine the effect of season, feeding niche, number of vegetation types, home range size, and fences on the number of exponential distributions observed. When animals faced the trade-off between forage quality and quantity during the dry season, they moved further between forage areas and water sources in order to get to better forage, which added to the number of movement scales observed. Elephants had a lower number of movement scales, compared to all the other feeding types, which could be attributed to them being able to switch between browse and graze. The number of movement scales increased in more heterogeneous areas. Animals with larger home ranges, which are also larger species, and animals more restricted by fences, had fewer movement scales. In order for managers to effectively manage protected areas and associated biodiversity they need take cognisance of the different scales animals operate under, and the different factors that may be important for different species.Peer reviewe

Four models of HIV counseling and testing: utilization and test results in South Africa.

BACKGROUND: HIV Counseling and Testing (HCT) is the point-of-entry for pathways of HIV care and prevention. However, HCT is not reaching many who are HIV infected and this may be related to the HCT provision model. We describe HCT utilization and HIV diagnosis using four models of HCT delivery: clinic-based, urban mobile, rural mobile, and stand-alone. METHODS: Using cross-sectional data from routine HCT provided in South Africa, we described client characteristics and HIV test results from information collected during service delivery between January 2009 and June 2012. RESULTS: 118,358 clients received services at clinic-based units, 18,597; stand-alone, 28,937; urban mobile, 38,840; and rural mobile, 31,984. By unit, clients were similar in terms of median age (range 28-31), but differed in sex distribution, employment status, prior testing, and perceived HIV risk. Urban mobile units had the highest proportion of male clients (52%). Rural mobile units reached the highest proportion of clients with no prior HCT (61%) and reporting no perceived HIV risk (64%). Overall, 10,862 clients (9.3%) tested HIV-positive. CONCLUSIONS: Client characteristics varied by HCT model. Importantly, rural and urban mobile units reached more men, first-time testers, and clients who considered themselves to be at low risk for HIV

Comparison of Xpert MTB/RIF with Other Nucleic Acid Technologies for Diagnosing Pulmonary Tuberculosis in a High HIV Prevalence Setting: A Prospective Study

In this prospective, real-world cohort study nested within a national screening program for tuberculosis, Lesley Scott and colleagues compare the performance of Xpert MTB/RIF on a single sputum sample with different TB sputum detection technologies

Large herbivores may alter vegetation structure of semi-arid savannas through soil nutrient mediation

In savannas, the tree–grass balance is governed by water, nutrients, fire and herbivory, and their interactions. We studied the hypothesis that herbivores indirectly affect vegetation structure by changing the availability of soil nutrients, which, in turn, alters the competition between trees and grasses. Nine abandoned livestock holding-pen areas (kraals), enriched by dung and urine, were contrasted with nearby control sites in a semi-arid savanna. About 40 years after abandonment, kraal sites still showed high soil concentrations of inorganic N, extractable P, K, Ca and Mg compared to controls. Kraals also had a high plant production potential and offered high quality forage. The intense grazing and high herbivore dung and urine deposition rates in kraals fit the accelerated nutrient cycling model described for fertile systems elsewhere. Data of a concurrent experiment also showed that bush-cleared patches resulted in an increase in impala dung deposition, probably because impala preferred open sites to avoid predation. Kraal sites had very low tree densities compared to control sites, thus the high impala dung deposition rates here may be in part driven by the open structure of kraal sites, which may explain the persistence of nutrients in kraals. Experiments indicated that tree seedlings were increasingly constrained when competing with grasses under fertile conditions, which might explain the low tree recruitment observed in kraals. In conclusion, large herbivores may indirectly keep existing nutrient hotspots such as abandoned kraals structurally open by maintaining a high local soil fertility, which, in turn, constrains woody recruitment in a negative feedback loop. The maintenance of nutrient hotspots such as abandoned kraals by herbivores contributes to the structural heterogeneity of nutrient-poor savanna vegetation