Supporting and retaining Village Health Teams: an assessment of a community health worker program in two Ugandan districts.

BACKGROUND: Uganda's national community health worker program involves volunteer Village Health Teams (VHTs) delivering basic health services and education. Evidence demonstrates their positive impact on health outcomes, particularly for Ugandans who would otherwise lack access to health services. Despite their impact, VHTs are not optimally supported and attrition is a growing problem. In this study, we examined the support needs and existing challenges of VHTs in two Ugandan districts and evaluated specific factors associated with long-term retention. We report on findings from a standardized survey of VHTs and exploratory interviews with key stakeholders and draw conclusions that inform efforts to strengthen and sustain community health care delivery in Uganda. METHODS: A mixed-methods approach was employed through a survey of 134 individual VHT members and semi-structured interviews with six key stakeholders. Descriptive and bivariate regression analysis of quantitative survey data was performed along with thematic analysis of qualitative data from surveys and interviews. In the regression analysis, the dependent variable is 10-year anticipated longevity among VHTs, which asked respondents if they anticipate continuing to volunteer as VHTs for at least 10 more years if their current situation remains unchanged. RESULTS: VHTs desire additional support primarily in the forms of money (e.g. transportation allowance) and material supplies (e.g. rubber boots). VHTs commonly report difficult working conditions and describe a lack of respect from their communities and other health workers. If their current situation remains unchanged, 57% of VHTs anticipate remaining in their posts for at least 10 years. Anticipated 10-year longevity was positively associated with stronger partnerships with local health center staff and greater ease in home visiting. CONCLUSIONS: Supporting and retaining Uganda's VHTs would be enhanced by building stronger partnerships between VHTs and other health workers and regularly providing supplies and transportation allowances. Pursuing such measures would likely improve equity in access to healthcare for all Ugandans.

Photodynamic antimicrobial polymers for infection control.

Hospital-acquired infections pose both a major risk to patient wellbeing and an economic burden on global healthcare systems, with the problem compounded by the emergence of multidrug resistant and biocide tolerant bacterial pathogens. Many inanimate surfaces can act as a reservoir for infection, and adequate disinfection is difficult to achieve and requires direct intervention. In this study we demonstrate the preparation and performance of materials with inherent photodynamic, surface-active, persistent antimicrobial properties through the incorporation of photosensitizers into high density poly(ethylene) (HDPE) using hot-melt extrusion, which require no external intervention except a source of visible light. Our aim is to prevent bacterial adherence to these surfaces and eliminate them as reservoirs of nosocomial pathogens, thus presenting a valuable advance in infection control. A two-layer system with one layer comprising photosensitizer-incorporated HDPE, and one layer comprising HDPE alone is also described to demonstrate the versatility of our approach. The photosensitizer-incorporated materials are capable of reducing the adherence of viable bacteria by up to 3.62 Log colony forming units (CFU) per square centimeter of material surface for methicillin resistant Staphylococcus aureus (MRSA), and by up to 1.51 Log CFU/cm(2) for Escherichia coli. Potential applications for the technology are in antimicrobial coatings for, or materials comprising objects, such as tubing, collection bags, handrails, finger-plates on hospital doors, or medical equipment found in the healthcare setting.

Effect of Bridging Anions on the Structure and Stability of Phenoxide Bridged Zinc Dipicolylamine Coordination Complexes.

A series of four related phenol derivatives, with 2,2'-dipicolylamine substituents at the ortho positions, were prepared and their Zn2+ coordination complexes studied by spectroscopic methods. X-ray crystal diffraction analysis of a dinuclear zinc complex with two bridging acetate anions showed a ternary structure with highly charged interior and lipophilic exterior, which helps explain why this class of water-soluble complexes can effectively diffuse through cell membranes. The stability of the dinuclear zinc complexes in aqueous solution was found to be strongly anion dependent; that is, bridging oxyanions, such as acetate and pyrophosphate, lock the two Zn2+ cations to the surrounding ligand and greatly enhance ligand/zinc affinity. Overall, the results provide new insight into the structural and mechanistic factors that control the recognition and chemosensing performance of phenoxide bridged dipicolylamine molecular probes.

Evaluation of fluorescent phosphatidylserine substrates for the aminophospholipid flippase in mammalian cells.

A series of fluorescent phosphatidylserine and phosphatidylcholine derivatives were prepared and evaluated by cell microscopy for ability to translocate across mammalian plasma membranes via the putative aminophospholipid flippase. Phosphatidylserine derivatives, with either a neutral 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) or a coumarin fluorophore appended to the 2-acyl chain, entered the cytosol of all three cell lines tested and control experiments showed that the translocation was due to flippase activity. In contrast, a phosphatidylserine conjugate containing a charged and polar carboxyfluorescein was not translocated and remained in the cell plasma membrane. The phosphatidylserine-coumarin derivative exhibits bright fluorescence and higher photostability than the NBD analogues, and thus is a promising new fluorescent probe for extended-imaging studies of flippase action in living cells using laser confocal microscopes.

Membrane transporters for anions that use a relay mechanism.

A new type of synthetic membrane transporter is described and shown to operate in vesicles by a relay mechanism. The transporter structure is a phosphatidylcholine derivative with a urea group appended to the end of its sn-2 acyl chain. The urea can bind a chloride ion at the membrane surface via hydrogen bonds and then relay it through the bilayer interior to an acceptor molecule located in the opposite membrane leaflet. Three phosphatidylcholine derivatives were studied and transport rates increased with transporter affinity for chloride. The results of various controls studies are consistent with an anion countertransport process using a relay mechanism and a kinetically active aggregate of two or four transporter molecules. Transport is inhibited if the transporter resides in only one leaflet of the membrane, if the bilayer is too thick, and if the counteranion is sulfate dianion. The expected favorable formulation properties of these amphiphilic compounds should facilitate efforts to transform them into tools for biomedical research and perhaps as therapeutic agents.

Bio-orthogonal phosphatidylserine conjugates for delivery and imaging applications.

The syntheses of phosphatidylserine (PS) conjugates are described, including fluorescent derivatives for potential cellular delivery and bioimaging applications. Installation of terminal functional groups (amine, thiol, or alkyne) onto the sn-2 chain provides reactive sites for bio-orthogonal conjugation of cargo with suitably protected PS derivatives. An amine-containing PS forms amide bonds with peptidic cargo, a thiol derivative is designed for conjugation to cargo that contain alpha-halo carbonyls or Michael acceptors, and the terminal alkyne PS analogue permits "click" conjugation with any azide-tagged molecule. This latter conjugation method is quite versatile as it can be performed without PS headgroup protection, in aqueous media, and with acid-labile cargo.

Zinc(II) coordination complexes as membrane-active fluorescent probes and antibiotics.

Molecular probes with zinc(II)-(2,2'-dipicolylamine) coordination complexes associate with oxyanions in aqueous solution and target biomembranes that contain anionic phospholipids. This study examines a new series of coordination complexes with 2,6-bis(zinc(II)-dipicolylamine)phenoxide as the molecular recognition unit. Two lipophilic analogues are observed to partition into the membranes of zwitterionic and anionic vesicles and induce the transport of phospholipids and hydrophilic anions (carboxyfluorescein). These lipophilic zinc complexes are moderately toxic to mammalian cells. A more hydrophilic analogue does not exhibit mammalian cell toxicity (LD(50) >50 microg mL(-1)), but it is highly active against the Gram-positive bacteria Staphylococcus aureus (MIC of 1 microg mL(-1)). Furthermore, it is active against clinically important S. aureus strains that are resistant to various antibiotics, including vancomycin and oxacillin. The antibiotic action is attributed to its ability to depolarize the bacterial cell membrane. The intense bacterial staining that was exhibited by a fluorescent conjugate suggests that this family of zinc coordination complexes can be used as molecular probes for the detection and imaging of bacteria.

Phosphatidylcholine-derived bolaamphiphiles via click chemistry.

The copper-catalyzed azide alkyne cycloaddition is employed to modify phosphatidylcholine precursors with sn-2 acyl chains containing terminal alkyne or azide groups. Although the reactions are conducted as biphasic dispersions, the yields are essentially quantitative. Bolaamphiphiles are formed by simply clicking together two phosphatidylcholine alkyne precursors to a central bisazide scaffold. The chemistry introduces polar 1,4-triazole units into the lipophilic region of the bilayer membrane, and the bolaamphiphiles do not form stable vesicles. [structure: see text].

Anion-mediated phase transfer of Zinc(II)-coordinated tyrosine derivatives.

[reaction: see text] Tyrosine-derived Zn(2+) coordination complexes and their fluorescent NBD conjugates are synthesized in a short, high-yielding procedure. The Zn(2+) complexes are highly water soluble, but in the presence of sodium laurate they readily transfer into an octanol layer. Furthermore, the NBD-labeled bis-Zn(2+) complex can partition into vesicle membranes containing anionic phospholipids.