Access to CD4 Testing for Rural HIV Patients: Findings from a Cohort Study in Zimbabwe

Background

CD4 cell count measurement remains an important diagnostic tool for HIV care in developing countries. Insufficient laboratory capacity in rural Sub-Saharan Africa is frequently mentioned but data on the impact at an individual patient level are lacking. Urban-rural discrepancies in CD4 testing have not been quantified to date. Such evidence is crucial for public health planning and to justify new yet more expensive diagnostic procedures that could circumvent access constraints in rural areas.

Objective

To compare CD4 testing among rural and urban HIV patients during the first year of treatment.

Methods

Records from 2,145 HIV positive adult patients from a Médecins sans Frontières (Doctors without Borders) HIV project in Beitbridge, Zimbabwe, during 2011 and 2012 were used for a retrospective cohort analysis. Covariate-adjusted risk ratios were calculated to estimate the effects of area of residence on CD4 testing at treatment initiation, six and 12 months among rural and urban patients.

Findings

While the proportion of HIV patients returning for medical consultations at six and 12 months decreased at a similar rate in both patient groups, CD4 testing during consultations dropped to 21% and 8% for urban, and 2% and 1% for rural patients at six and 12 months, respectively. Risk ratios for missing CD4 testing were 0.8 (95% CI 0.7-0.9), 9.2 (95% CI 5.5-15.3), and 7.6 (95% 3.7-17.1) comparing rural versus urban patients at treatment initiation, six and 12 months, respectively.

Conclusions

CD4 testing was low overall, and particularly poor in rural patients. Difficulties with specimen transportation were probably a major factor underlying this difference and requires new diagnostic approaches. Our findings point to severe health system constraints in providing CD4 testing overall that need to be addressed if effective monitoring of HIV patients is to be achieved, whether by alternative CD4 diagnostics or newly-recommended routine viral load testing.     

Someone Who Cares: Evaluation of School Advisor Programs in Two Community Settings

In investigative interviews concerned with allegations of sexual abuse, open-ended prompts by interviewers elicit more information than focused prompts. We attempted to explore these effects in investigations of physical abuse. Interviews with 50 children from 2 age groups (5–6-year-olds, 9–10-year-olds) who made subsequently substantiated allegations of physical abuse by their parents were subjected to detailed psycholinguistic analysis. The overall productivity (number of words spoken) and informativeness (number of details elicited) of these children were remarkably low. The children were also relatively unresponsive to the investigators' individual utterances, and many of the interviewers' utterances were nonsubstantive (15%). The interviewers were more likely than those included in studies of sexual abuse investigations to use open-ended as opposed to focused prompts. These open-ended utterances elicited significantly more words but not more details than focused prompts. Older children also provided longer and richer utterances than younger children. The discussion examines the reasons why open-ended utterances appear less fruitful in investigations of physical as opposed to sexual abuse.     

Metabolomic Analysis in Severe Childhood Pneumonia in The Gambia,West Africa: Findings from a Pilot Study

Background

Pneumonia remains the leading cause of death in young children globally and improved diagnostics are needed to better identify cases and reduce case fatality. Metabolomics, a rapidly evolving field aimed at characterizing metabolites in biofluids, has the potential to improve diagnostics in a range of diseases. The objective of this pilot study is to apply metabolomic analysis to childhood pneumonia to explore its potential to improve pneumonia diagnosis in a high-burden setting.

Methodology/Principal Findings

Eleven children with World Health Organization (WHO)-defined severe pneumonia of non-homogeneous aetiology were selected in The Gambia, West Africa, along with community controls. Metabolomic analysis of matched plasma and urine samples was undertaken using Ultra Performance Liquid Chromatography (UPLC) coupled to Time-of-Flight Mass Spectrometry (TOFMS). Biomarker extraction was done using SIMCA-P⁺ and Random Forests (RF). ‘Unsupervised’ (blinded) data were analyzed by Principal Component Analysis (PCA), while ‘supervised’ (unblinded) analysis was by Partial Least Squares-Discriminant Analysis (PLS-DA) and Orthogonal Projection to Latent Structures (OPLS). Potential markers were extracted from S-plots constructed following analysis with OPLS, and markers were chosen based on their contribution to the variation and correlation within the data set. The dataset was additionally analyzed with the machine-learning algorithm RF in order to address issues of model overfitting and markers were selected based on their variable importance ranking. Unsupervised PCA analysis revealed good separation of pneumonia and control groups, with even clearer separation of the groups with PLS-DA and OPLS analysis. Statistically significant differences (p<0.05) between groups were seen with the following metabolites: uric acid, hypoxanthine and glutamic acid were higher in plasma from cases, while L-tryptophan and adenosine-5′-diphosphate (ADP) were lower; uric acid and L-histidine were lower in urine from cases. The key limitation of this study is its small size.

Conclusions/Significance

Metabolomic analysis clearly distinguished severe pneumonia patients from community controls. The metabolites identified are important for the host response to infection through antioxidant, inflammatory and antimicrobial pathways, and energy metabolism. Larger studies are needed to determine whether these findings are pneumonia-specific and to distinguish organism-specific responses. Metabolomics has considerable potential to improve diagnostics for childhood pneumonia.     

Evaluation of a Non-Destructive Method for Measuring Turgor Pressure in Helianthus

The portable instrument described by Heathcote, Etherington,and Woodward (1979) for the non-destructive measurement of turgorpressure was evaluated in Helianthus annuus and Helianthus paradoxus.A good correlation was obtained between turgor pressure measuredwith the instrument and turgor pressure estimated by the pressure-volumetechnique for individual leaves allowed to dry after excision;however, variation in both the intercept and slope of the relationshipoccurred between leaves. Consequently, there was no correlationbetween the output of the instrument for individual leaves andthe turgor pressure of the same leaves estimated by conventionalmethods. Moreover, for a given leaf, the instrument had onlya limited ability to detect temporal variation in turgor pressurewhen compared with turgor pressure calculated from measuredvalues of leaf water potential and leaf osmotic potential. Theinstrument's output was influenced by its proximity to majorveins and by leaf thickness. We conclude that variability inleaf thickness and the presence of large veins limits its usefulnessfor measurement of turgor pressure in Helianthus. Key words: Leaf thickness, Turgormeter, Turgor pressure, Helianthus     

Transitioning a Large Scale HIV/AIDS Prevention Program to Local Stakeholders: Findings from the Avahan Transition Evaluation

Background

Between 2009–2013 the Bill and Melinda Gates Foundation transitioned its HIV/AIDS prevention initiative in India from being a stand-alone program outside of government, to being fully government funded and implemented. We present an independent prospective evaluation of the transition.

Methods

The evaluation drew upon (1) a structured survey of transition readiness in a sample of 80 targeted HIV prevention programs prior to transition; (2) a structured survey assessing institutionalization of program features in a sample of 70 targeted intervention (TI) programs, one year post-transition; and (3) case studies of 15 TI programs.

Findings

Transition was conducted in 3 rounds. While the 2009 transition round was problematic, subsequent rounds were implemented more smoothly. In the 2011 and 2012 transition rounds, Avahan programs were well prepared for transition with the large majority of TI program staff trained for transition, high alignment with government clinical, financial and managerial norms, and strong government commitment to the program. One year post transition there were significant program changes, but these were largely perceived positively. Notable negative changes were: limited flexibility in program management, delays in funding, commodity stock outs, and community member perceptions of a narrowing in program focus. Service coverage outcomes were sustained at least six months post-transition.

Interpretation

The study suggests that significant investments in transition preparation contributed to a smooth transition and sustained service coverage. Notwithstanding, there were substantive program changes post-transition. Five key lessons for transition design and implementation are identified.     

Changes in HIV Outcomes Following Depression Care in a Resource-Limited Setting: Results from a Pilot Study in Bamenda,Cameroon

Background

Little is known about how improved depression care affects HIV-related outcomes in Africa. In a sample of depressed HIV patients in a low income, sub-Saharan country, we explored how implementing measurement-based antidepressant care (MBC) affected HIV outcomes over 4 months of antidepressant treatment.

Methods

As part of a project adapting MBC for use in Cameroon, we enrolled 41 depressed HIV patients on antiretroviral therapy in a pilot study in which a depression care manager (DCM) provided an outpatient HIV clinician with evidence-based decision support for antidepressant treatment. Acute depression management was provided for the first 12 weeks, with DCM contact every 2 weeks and HIV clinician appointments every 4 weeks. We measured HIV clinical and psychiatric outcomes at 4 months.

Results

Participants were moderately depressed at baseline (mean Patient Health Questionnaire [PHQ] score = 14.4, range 13.1, 15.6). All HIV clinical outcomes improved by four month follow-up: mean (range) CD4 count improved from 436 (2, 860) to 452 (132, 876), mean (range) log-viral load decreased from 4.02 (3.86, 4.17) to 3.15 (2.81, 3.49), the proportion with virologic suppression improved from 0% to 18%, mean (range) HIV symptoms decreased from 6.4 (5.5, 7.3) to 3.1 (2.5, 3.7), the proportion reporting good or excellent health improved from 18% to 70%, and the proportion reporting any missed ARV doses in the past month decreased from 73% to 55%. Concurrently, psychiatric measures improved. The mean (range) PHQ score decreased from 14.4 (13.1, 15.6) to 1.6 (0.8, 2.4) and 90% achieved depression remission, while mean maladaptive coping style scores decreased and mean adaptive coping scores and self-efficacy scores improved.

Conclusion

In this pilot study of an evidence-based depression treatment intervention for HIV-infected patients in Cameroon, a number of HIV behavioral and non-behavioral health outcomes improved over 4 months of effective depression treatment. These data are consistent with the hypothesis that better depression care can lead to improved HIV outcomes.     

Validity and Reliability of Using a Self-Lavaging Device for Cytology and HPV Testing for Cervical Cancer Screening: Findings from a Pilot Study

Self-sampling could increase cervical cancer screening uptake. While methods have been identified for human papillomavirus (HPV) testing, to date, self-sampling has not provided adequate specimens for cytology. We piloted the validity and reliability of using a self-lavaging device for cervical cytology and HPV testing. We enrolled 198 women in New York City in 2008–2009 from three ambulatory clinics where they received cervical cancer screening. All were asked to use the Delphi Screener™ to self-lavage 1–3 months after clinician-collected index cytological smear (100 normal; 98 abnormal). Women with abnormal cytology results from either specimen underwent colposcopy; 10 women with normal results from both specimens also underwent colposcopy. We calculated sensitivity of self-collected cytology to detect histologically confirmed high grade lesions (cervical intraepithelial neoplasia, CIN, 2+); specificity for histology-negative (CIN 1 or lower), paired cytology negative, or a third cytology negative; and kappa for paired results. One hundred and ninety-seven (99.5%) women self-collected a lavage. Seventy-five percent had moderate to excellent cellularity, two specimens were unsatisfactory for cytology. Seven of 167 (4%) women with definitive results had CIN2+; one had normal and six abnormal cytology results with the self-lavage (sensitivity = 86%, 95% Confidence Interval, CI: 42, 100). The kappa for paired cytology was low (0.36; 95% CI: 0.25, 0.47) primarily due to clinician specimens with atypical squamous cells of undetermined significance (ASC-US) and low grade squamous intraepithelial lesion (LSIL) coded as normal using Screener specimens. However, three cases of HSIL were coded as ASC-US and one as normal using Screener specimens. Seventy-three women had paired high-risk HPV tests with a kappa of 0.66 (95% CI: 0.49, 0.84). Based on these preliminary findings, a larger study to estimate the performance of the Screener for co-testing cytology and HPV or for HPV testing with cytology triage is warranted.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00702208","term_id":"NCT00702208"}}NCT00702208     

An Elliptometer: A Simple Method of Measuring the Areas of Structures in Microscopic Sections

A simple method of measuring the cross sectional areas of objects (such as cells) in microscopic sections is described. A beam of light is passed through an adjustable diaphragm and focussed by a lens on a screen of mm. ruled graph paper. The screen may be rotated about a horizontal axis. Adjustment of the aperture of the diaphragm and the plane of the screen yields illuminated areas of variable size and degree of ellipticity. As close a “fit” as possible is made between the illuminated area and the camera lucida tracing of the object to be measured. The lengths of the major and minor axes of the appropriate ellipse are read from the screen. The application of the formula for the area of an ellipse to mean major and minor axes for a group of cells gives the mean cross sectional area for the cell population under investigation.     

Measuring Access to Medicines: A Survey of Prices,Availability and Affordability in Shaanxi Province of China

Objective

To measure the prices and availability of selected medicines in Shaanxi Province after the implementation of new healthcare reform in 2009.

Methods

Data on the prices and availability of 47 medicines were collected from 50 public and 36 private sector medicine outlets in six regions of Shaanxi Province, Western China using a standardized methodology developed by the World Health Organization and Health Action International from September to October 2010. Medicine prices were compared with international reference prices to obtain a median price ratio. Affordability was measured as the number of days’ wages required for the lowest-paid unskilled government worker to purchase standard treatments for common conditions.

Findings

The mean availabilities of originator brands and lowest-priced generics were 8.9% and 26.5% in the public sector, and 18.1% and 43.6% in the private sector, respectively. The public sector procured generics and originator brands at median price ratios of 0.75 and 8.49, respectively, while patients paid 0.97 and 10.16. Final patient prices for lowest-priced generics and originator brands in the private sector were about 1.53 and 8.36 times their international retail prices, respectively. Public sector vendors applied high markups of 30.4% to generics, and 19.6% to originator brands. In the private sector, originator brands cost 390.7% more, on average, than their generic equivalents. Generic medicines were priced 17.3% higher in the private sector than the public sector. The lowest-paid government worker would need 0.1 day’s wages to purchase captopril for lowest-priced generics from private sector, while 6.6 days’ wages for losartan. For originator brands, the costs rise to 1.2 days’ wages for salbutamol inhaler and 15.6 days’ wages for omeprazole.

Conclusions

The prices, availability and affordability of medicines in China should be improved to ensure equitable access to basic medical treatments, especially for the poor. This requires multi-faceted interventions, as well as the review and refocusing of policies, regulations and educational interventions.     

Acetylcholine Release from Isolated Synaptic Vesicles Related to Ionic Permeability Changes: Continuous Detection with a Chemiluminescent Method

The effect of ionic permeability changes on acetylcholine (ACh) release from isolated cholinergic synaptic vesicles of Torpedo was studied using a chemiluminescent method for continuous ACh detection. Vesicles rendered freely permeable to potassium by valinomycin lost most of their ACh content in K+ media, if the accompanying anion was permeant; it thus appeared that ACh leakage occurred as the result of internal osmotic changes. Upon addition of ionophores that catalyse monovalent cation/H+ exchange (gramicidin D or a mixture of valinomycin plus protonophore FCCP), a rapid but transient ACh release was observed. Surprisingly, nigericin which also catalyses K+/H+ exchange, had no effect on ACh release. The divalent cation ionophore A23187 promoted ACh release only when calcium (and not magnesium) was introduced into the external medium in a millimolar concentration range. As the simultaneous addition of the protonophore FCCP and A23187 decreased this calcium-dependent ACh leakage, a releasing effect of A23187 through Ca2+/H+ exchange is suspected. The present results emphasise the role of internal protons for ACh retention inside synaptic vesicles.     

Association of MicroRNA-196a2 Variant with Response to Short-Acting β2-Agonist in COPD: An Egyptian Pilot Study

Chronic obstructive pulmonary disease (COPD) is a multifactorial chronic respiratory disease, characterized by an obstructive pattern. Understanding the genetic predisposition of COPD is essential to develop personalized treatment regimens. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that modulate the expression levels of specific proteins based on sequence complementarity with their target mRNA molecules. Emerging evidences demonstrated the potential use of miRNAs as a disease biomarker. This pilot study aimed to investigate the association of the MIR-196a2 rs11614913 (C/T) polymorphism with COPD susceptibility, the clinical outcome and bronchodilator response to short-acting β₂-agonist. Genotyping of rs11614913 polymorphism was determined in 108 COPD male patients and 116 unrelated controls using real-time polymerase chain reaction technology. In silico target prediction and network core analysis were performed. COPD patients did not show significant differences in the genotype distribution (p = 0.415) and allele frequencies (p = 0.306) of the studied miRNA when compared with controls. There were also no associations with GOLD stage, dyspnea grade, disease exacerbations, COPD assessment test for estimating impact on health status score, or the frequency of intensive care unit admission. However, COPD patients with CC genotype corresponded to the smallest bronchodilator response after Salbutamol inhalation, the heterozygotes (CT) had an intermediate response, while those with the TT genotype showed the highest response (p < 0.001). In conclusion MIR-196a2 rs11614913 polymorphism is associated with the bronchodilator response of COPD in our sample of the Egyptian population, generating hypothesis of the potential use of MIR-196a2 variant as a pharmacogenetic marker for COPD.     

Potential of Transgenic Crops in Bangladesh: Findings from a Consultation of Bangladeshi Scientific Experts

This note summarizes the results of a consultation of scientific and regulatory experts in July 2005 on the potential of transgenic crops in Bangladesh. We find that Bangladeshi experts are optimistic on the potential of agricultural biotechnology to respond to biotic and abiotic stresses in their country in the future. Public research is constrained by human capacities, infrastructure and capital investment, and transgenic crop development will require the active involvement of outside partners, such as international organizations or collaboration with private companies. We also find that social acceptance of genetic engineering is not considered a major issue, but could become one, and prompted experts to call for a wider awareness campaign on the technology.This research project was conducted as part of the South Asia Biosafety Program (SABP), a project funded by the US Agency for International Development (USAID) and jointly managed by the International Food Policy Research Institute and AGBIOS Canada. The authors would like to thank the Bangladesh Agricultural Research Council and all the participants to the meetings in Dhaka and Mymensingh for their help.     

Development of a Learning-Oriented Computer Assisted Instruction Designed to Improve Skills in the Clinical Assessment of the Nutritional Status: A Pilot Evaluation

Computer assisted instruction (CAI) is an effective tool for evaluating and training students and professionals. In this article we will present a learning-oriented CAI, which has been developed for students and health professionals to acquire and retain new knowledge through the practice. A two-phase pilot evaluation was conducted, involving 8 nutrition experts and 30 postgraduate students, respectively. In each training session, the software developed guides users in the integral evaluation of a patient’s nutritional status and helps them to implement actions. The program includes into the format clinical tools, which can be used to recognize possible patient’s needs, to improve the clinical reasoning and to develop professional skills. Among them are assessment questionnaires and evaluation criteria, cardiovascular risk charts, clinical guidelines and photographs of various diseases. This CAI is a complete software package easy to use and versatile, aimed at clinical specialists, medical staff, scientists, educators and clinical students, which can be used as a learning tool. This application constitutes an advanced method for students and health professionals to accomplish nutritional assessments combining theoretical and empirical issues, which can be implemented in their academic curriculum.     

Urzymology: Experimental Access to a Key Transition in the Appearance of Enzymes

Urzymes are catalysts derived from invariant cores of protein superfamilies. Urzymes from both aminoacyl-tRNA synthetase classes possess sophisticated catalytic mechanisms: pre-steady state bursts, significant transition-state stabilization of both amino acid activation, and tRNA acylation. However, they have insufficient specificity to ensure a fully developed genetic code, suggesting that they participated in synthesizing statistical proteins. They represent a robust experimental platform from which to articulate and test hypotheses both about their own ancestors and about how they, in turn, evolved into modern enzymes. They help reshape numerous paradigms from the RNA World hypothesis to protein structure databases and allostery.     

Structural Barriers to Timely Initiation of Antiretroviral Treatment in Vietnam: Findings from Six Outpatient Clinics

In Vietnam, premature mortality due to AIDS-related conditions is commonly associated with late initiation to antiretroviral therapy (ART). This study explores reasons for late ART initiation among people living with HIV (PLHIV) from the perspectives of health care providers and PLHIV. The study was undertaken in six clinics from five provinces in Vietnam. Baseline CD4 counts were collected from patient records and grouped into three categories: very late initiators (≤100 cells/mm³ CD4), late initiators (100–200 cells/mm³) and timely initiators (200–350 cells/mm³). Thirty in-depth interviews with patients who started ART and 15 focus group discussions with HIV service providers were conducted and thematic analysis of the content performed. Of 934 patients, 62% started ART very late and 11% initiated timely treatment. The proportion of patients for whom a CD4 count was obtained within six months of their HIV diagnosis ranged from 22% to 72%. The proportion of patients referred to ART clinics by voluntary testing and counselling centres ranged from 1% to 35%. Structural barriers to timely ART initiation were poor linkage between HIV testing and HIV care and treatment services, lack of patient confidentiality and a shortage of HIV/AIDS specialists. If Vietnam’s treatment practice is to align with WHO recommendations then the connection between voluntary counselling and testing service and ART clinics must be improved. Expansion and decentralization of HIV/AIDS services to allow implementation at the community level increased task sharing between doctors and nurses to overcome limited human resources, and improved patient confidentiality are likely to increase timely access to HIV treatment services for more patients.     

Histological Evaluation of the Biocompatibility of Polyurea Crosslinked Silica Aerogel Implants in a Rat Model: A Pilot Study

Background

Aerogels are a versatile group of nanostructured/nanoporous materials with physical and chemical properties that can be adjusted to suit the application of interest. In terms of biomedical applications, aerogels are particularly suitable for implants such as membranes, tissue growth scaffolds, and nerve regeneration and guidance inserts. The mesoporous nature of aerogels can also be used for diffusion based release of drugs that are loaded during the drying stage of the material. From the variety of aerogels polyurea crosslinked silica aerogels have the most potential for future biomedical applications and are explored here.

Methodology

This study assessed the short and long term biocompatibility of polyurea crosslinked silica aerogel implants in a Sprague-Dawley rat model. Implants were inserted at two different locations a) subcutaneously (SC), at the dorsum and b) intramuscularly (IM), between the gluteus maximus and biceps femoris of the left hind extremity. Nearby muscle and other internal organs were evaluated histologically for inflammation, tissue damage, fibrosis and movement (travel) of implant.

Conclusion/Significance

In general polyurea crosslinked silica aerogel (PCSA) was well tolerated as a subcutaneous and an intramuscular implant in the Sprague-Dawley rat with a maximum incubation time of twenty months. In some cases a thin fibrous capsule surrounded the aerogel implant and was interpreted as a normal response to foreign material. No noticeable toxicity was found in the tissues surrounding the implants nor in distant organs. Comparison was made with control rats without any implants inserted, and animals with suture material present. No obvious or noticeable changes were sustained by the implants at either location. Careful necropsy and tissue histology showed age-related changes only. An effective sterilization technique for PCSA implants as well as staining and sectioning protocol has been established. These studies further support the notion that silica-based aerogels could be useful as biomaterials.     

The SHAZ! Project: Results from a Pilot Randomized Trial of a Structural Intervention to Prevent HIV among Adolescent Women in Zimbabwe

Adolescent females in Zimbabwe are at high risk for HIV acquisition. Shaping the Health of Adolescents in Zimbabwe (SHAZ!) was a randomized controlled trial of a combined intervention package including life-skills and health education, vocational training, micro-grants and social supports compared to life-skills and health education alone. SHAZ! was originally envisioned as a larger effectiveness trial, however, the intervention was scaled back due to contextual and economic conditions in the country at the time. SHAZ! enrolled 315 participants randomly assigned to study arm within blocks of 50 participants (158 intervention and 157 control). The intervention arm participants showed statistically significant differences from the control arm participants for several outcomes during the two years of follow up including; reduced food insecurity [IOR = 0.83 vs. COR = 0.68, p-0.02], and having their own income [IOR = 2.05 vs. COR = 1.67, p = 0.02]. Additionally, within the Intervention arm there was a lower risk of transactional sex [IOR = 0.64, 95% CI (0.50, 0.83)], and a higher likelihood of using a condom with their current partner [IOR = 1.79, 95% CI (1.23, 2.62)] over time compared to baseline. There was also evidence of fewer unintended pregnancies among intervention participants [HR = 0.61, 95% CI (0.37, 1.01)], although this relationship achieved only marginal statistical significance. Several important challenges in this study included the coordination with vocational training programs, the political and economic instability of the area at the time of the study, and the difficulty in creating a true standard of care control arm. Overall the results of the SHAZ! study suggest important potential for HIV prevention intervention packages that include vocational training and micro-grants, and lessons for further economic livelihoods interventions with adolescent females. Further work is needed to refine the intervention model, and test the impact of the intervention at scale on biological outcomes.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02034214","term_id":"NCT02034214"}}NCT02034214