Cryptococcal Meningitis Diagnostics and Screening in the Era of Point-of-Care Laboratory Testing.

Over the past ten years, standard diagnostics for cryptococcal meningitis in HIV-infected persons have evolved from culture to India ink to detection of cryptococcal antigen (CrAg), with the recent development and distribution of a point-of-care lateral flow assay. This assay is highly sensitive and specific in cerebrospinal fluid (CSF), but is also sensitive in the blood to detect CrAg prior to meningitis symptoms. CrAg screening of HIV-infected persons in the blood prior to development of fulminant meningitis and preemptive treatment for CrAg-positive persons are recommended by the World Health Organization and many national HIV guidelines. Thus, CrAg testing is occurring more widely, especially in resource-limited laboratory settings. CrAg titer predicts meningitis and death and could be used in the future to customize therapy according to burden of infection

Refinement Type Inference via Horn Constraint Optimization

We propose a novel method for inferring refinement types of higher-order functional programs. The main advantage of the proposed method is that it can infer maximally preferred (i.e., Pareto optimal) refinement types with respect to a user-specified preference order. The flexible optimization of refinement types enabled by the proposed method paves the way for interesting applications, such as inferring most-general characterization of inputs for which a given program satisfies (or violates) a given safety (or termination) property. Our method reduces such a type optimization problem to a Horn constraint optimization problem by using a new refinement type system that can flexibly reason about non-determinism in programs. Our method then solves the constraint optimization problem by repeatedly improving a current solution until convergence via template-based invariant generation. We have implemented a prototype inference system based on our method, and obtained promising results in preliminary experiments.Comment: 19 page

Conservation and “land grabbing” in rangelands: Part of the problem or part of the solution?

Large-scale land acquisitions have increased in scale and pace due to changes in commodity markets, agricultural investment strategies, land prices, and a range of other policy and market forces. The areas most affected are the global “commons” – lands that local people traditionally use collectively — including much of the world’s forests, wetlands, and rangelands. In some cases land acquisition occurs with environmental objectives in sight – including the setting aside of land as protected areas for biodiversity conservation. On the other hand, current trends and patterns of commercial land acquisition present a major and growing threat not just to local livelihoods and human rights, but also to conservation objectives. There is a potential opportunity here for greater collaboration between conservation interests, and local communities’ land rights interests with their supporters amongst human rights and social justice movements. This Issue Paper documents experiences from the rangelands of Mongolia, Kenya, India, Ethiopia, and other countries, which were presented at a Conference on Conservation and Land Grabbing held in London in 2013

A Comparison of Miltefosine and Sodium Stibogluconate for Treatment of Visceral Leishmaniasis in an Ethiopian Population with High Prevalence of HIV Infection.

BACKGROUND: Antimonials are the mainstay of visceral leishmaniasis (VL) treatment in Africa. The increasing incidence of human immunodeficiency virus (HIV) coinfection requires alternative safe and effective drug regimens. Oral miltefosine has been proven to be safe and effective in the treatment of Indian VL but has not been studied in Africa or in persons with HIV and VL coinfection. METHODS: We compared the efficacy of miltefosine and sodium stibogluconate (SSG) in the treatment of VL in persons in Ethiopia. A total of 580 men with parasitologically and/or serologically confirmed VL were randomized to receive either oral miltefosine (100 mg per day for 28 days) or intramuscular SSG (20 mg/kg per day for 30 days). RESULTS: The initial cure rate was 88% in both treatment groups. Mortality during treatment was 2% in the miltefosine group, compared with 10% in the SSG group. Initial treatment failure was 8% in the miltefosine group, compared with 1% in the SSG group. Among the 375 patients (65%) who agreed to HIV testing, HIV seroprevalence was 29%. Among patients not infected with HIV, initial cure, mortality, and initial treatment failure rates were not significantly different (94% vs. 95%, 1% vs. 3%, and 5% vs. 1% for the miltefosine and SSG groups, respectively). Initial treatment failure with miltefosine occurred in 18% of HIV-coinfected patients, compared with treatment failure in 5% of non-HIV-infected patients. At 6 months after treatment, 174 (60%) of the 290 miltefosine recipients and 189 (65%) of the 290 SSG recipients experienced cure; 30 (10%) of 290 in the miltefosine group and 7 (2%) of 290 in the SSG group experienced relapse, and the mortality rate was 6% in the miltefosine group, compared with 12% in the SSG group. HIV-infected patients had higher rates of relapse (16 [25%] of 63 patients), compared with non-HIV-infected patients (5 [5%] of 131). CONCLUSIONS: Treatment with miltefosine is equally effective as standard SSG treatment in non-HIV-infected men with VL. Among HIV-coinfected patients, miltefosine is safer but less effective than SSG

Determinants of health seeking behaviour following rabies exposure in Ethiopia

The objective of this study was to identify factors that determine medical treatment seeking behaviour following potential rabies exposure after being bitten by a suspected dog and the likelihood of compliance to receive sufficient doses of post-exposure prophylaxis after the visit to a health centre visit. A detailed survey based on case investigation was conducted on suspected rabid dog bite cases in three areas of Ethiopia. Two multivariable logistic regression models were created with a set of putative variables to explain treatment seeking and compliance outcomes. Based on the registered bite cases at each health centre and the set of unregistered bite cases derived by contact tracing, 655 bite victim cases were identified to have occurred between September 2013 and August 2014. Of these evaluated bite incidences, 465 cases were considered to have been caused by a potentially rabid dog. About 77% of these suspected rabid dog bite victims visited a health centre, while 57% received sufficient doses of PEP. The overall likelihood of seeking medical services following rabies exposure was higher for people bitten by dogs of unknown ownership, where the bite was severe, being bitten on the leg, spend of more than 100 USD per month and where the victim lived close to the nearest health centre, while the likelihood of receiving sufficient doses of PEP was sensitive to monthly spending and distance to health centre. However, the evaluated factors did only explain a part of the variation among the three districts. The district in which victims lived appeared to have a relevant influence on the likelihood of seeking medical treatment but did not improve the prediction on the likelihood of treatment compliance. Given the insights obtained from this study, improvements in the rural districts with regard to accessibility of post-exposure prophylaxis delivering health centres in shorter distance could improve health seeking behaviour. In addition, in rural districts, majority of exposed persons who seek medical treatment tend to comply with treatment regimen, indicating that the promotion of medical treatment through awareness creation campaigns could be beneficial

A randomized controlled trial of the effects of a prudent diet on cardiovascular risk factors, gene expression, and DNA methylation - the Diet and Genetic Intervention (DIGEST) Pilot study

Background Risk of cardiovascular disease (CVD) can be increased by single-nucleotide polymorphisms (SNPs) in the 9p21 region of the genome. However, observational studies have shown that the deleterious effect of 9p21 SNPs on CVD might be offset by consuming a diet rich in fresh fruits and vegetables. This association may be driven by diet-influenced modifications in epigenetic and gene expression profiles. In this pilot study, we aimed to: i. test the feasibility of provision of a ‘Prudent’ and ‘Western’ diet outside of a specialized clinic, ii. assess the impact of each diet on cardiovascular risk factors. Methods A single centre, parallel two-arm, pilot randomized controlled trial (RCT) with food provision was conducted in a university teaching hospital outpatient clinic (McMaster university, Hamilton, ON, Canada). The aim was to recruit 80 participants, which allowed for a 10 % dropout. The actual study consisted of 84 apparently healthy participants (69 % women, 18 to 77 years) at low cardiovascular risk. Participants were randomly assigned to follow one of two weight-maintaining diets: ‘Prudent’ or ‘Western’ for 2-weeks. The Prudent diet provided 92 % of provided food consumed). The Prudent diet was 48 % more palatable than the Western diet (P < 0.05). Participants receiving the Prudent diet showed a trend toward reduced systolic (-4 mmHg; P = 0.10) and diastolic (-3 mmHg; P = 0.07) blood pressure, and total cholesterol (-0.24 mmol/L; P = 0.08), compared to individuals receiving the Western diet. Data collection from all randomized participants was completed within 18 months. Conclusions Recruitment, and retention of apparently healthy, normotensive adults into a feeding study for a 2-week duration is feasible outside of specialized dietary clinic, and modest diet-related changes in biomarkers begin to appear after two weeks

Patients-to-healthcare workers HIV transmission risk from sharp injuries, Southern Ethiopia

Background: Accidental needlestick injury rate among healthcare workers in Hawassa is extremely high. Epidemiological findings proved the infectious potential of this injury contaminated with a Human&#160; Immunodeficiency Virus (HIV)-infected patient&#8217;s blood.Objective: This study aimed at estimating the risk of HIV transmission from patients to healthcare workers in Hawassa City, Ethiopia.Method: A probabilistic risk model was employed. Scenario-based assumptions were made for the values of parameters following areview of published reports between 2007 and 2010.Parameters: HIV prevalence, needlestick injury rate, exposure rate, sero-conversion rate, risk of HIV transmission and cumulative risk of HIV transmission.Finding: Generally, healthcare workers in Hawassa are considered to be at a relatively low (0.0035%) occupational risk of contracting HIV &#8211; less than 4 in 100,000 of healthcare workers in the town (1 in 28,751 workers a year). The 30 years&#8217; maximum cumulative risk estimate is approximately five healthcare workers per 1000 workers in the study area. Still, this small number should be considered a serious matter requiring post-exposure prophylaxis following exposure to unsafe medical practice leading to HIV infection

Grain yield, stem borer and disease resistance of new maize hybrids in Kenya

Evaluation of 30 maize hybrids for yield and resistance to stem borers and foliar diseases in four agroecologies in Kenya was conducted in 2009. There were significant differences among the hybrids in leaf damage, number of exit holes, tunnel length and grain yield in Kiboko. The maize hybrids CKPH08014, CKPH08025, and CKPH08026 showed the least leaf damage, exit holes and tunnel length, similar to the resistant check. Although ten hybrids yielded over 8 t/ha, two hybrids, CKPH09001 and CKPH08033, gave the highest yield of 8.99 and 8.86 t/ha, respectively, in Kiboko. There were significant differences among the hybrids in resistance to leaf rust and maize streak virus in Kakamega. The intensity of foliar diseases was high in Kakamega compared to the other sites. All hybrids appeared resistant to the foliar diseases at Kakamega. On the average, the highest yield of the hybrids was recorded in Kiboko (7.5 t/ha) followed by Kakamega (6.1 t/ha), and the least at Embu (3.5 t/ha), and Mtwapa (3.14 t/ha). The performance of the hybrids varied from site to site, with CKPH09002 and CKPH09003 performing well at Mtwapa, CKPH09001 at Kiboko, CKPH08039 at Embu, CKPH 08002 and CKPH08010 at Kakamega.Key words: Host plant resistance, maize, pest management, stem borer, foliar disease

Na-K-Cl Cotransporter-1 as a Regulator of Manganese-induced Astrocyte Swelling

Astrocyte swelling leads to brain edema, intracranial pressure, brain herniation and acute liver failure (fulminant hepatic failure) which is the major cause of death in this condition. Manganese has been strongly implicated as an important factor in astrocyte swelling. Manganese in excess is neurotoxic and causes a CNS disorder that resembles  Parkinson¡¦s disease (manganism). Manganese highly accumulates in astrocytes, which renders these cells more vulnerable to its toxicity. In addition to manganism, increased brain levels of manganese have been found in hepatic encephalopathy. Manganese is known to cause cellswelling in cultured astrocytes, although the means by which this occurs has not been fully elucidated. A disturbance in one or more of these systems may result in loss of ion homeostasis and cell swelling. In particular, activation of the Na-K-Cl cotransporter-1 (NKCC1) has been shown to be involved in cell swelling in several neurological disorders.We therefore examined the effect of manganese on NKCC activity and its potential role in the swelling of astrocytes. Cultured astrocytes were exposed to manganese (50 µM), and NKCC activity was measured. Manganese increased NKCC activity at 24 h. Inhibition of this  activity by bumetanide diminished manganese-induced astrocyte swelling.  Manganese (Mn) also increased total as well as phosphorylated NKCC1. These results suggest that activation of NKCC1 is an important factor in the mediation of astrocyte swelling by manganese and that such activation appears to be mediated by NKCC1 abundance

Future and potential spending on health 2015-40: Development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Background: The amount of resources, particularly prepaid resources, available for health can affect access to health care and health outcomes. Although health spending tends to increase with economic development, tremendous variation exists among health financing systems. Estimates of future spending can be beneficial for policy makers and planners, and can identify financing gaps. In this study, we estimate future gross domestic product (GDP), all-sector government spending, and health spending disaggregated by source, and we compare expected future spending to potential future spending. Methods: We extracted GDP, government spending in 184 countries from 1980-2015, and health spend data from 1995-2014. We used a series of ensemble models to estimate future GDP, all-sector government spending, development assistance for health, and government, out-of-pocket, and prepaid private health spending through 2040. We used frontier analyses to identify patterns exhibited by the countries that dedicate the most funding to health, and used these frontiers to estimate potential health spending for each low-income or middle-income country. All estimates are inflation and purchasing power adjusted. Findings: We estimated that global spending on health will increase from US$9.21 trillion in 2014 to$24.24 trillion (uncertainty interval [UI] 20.47-29.72) in 2040. We expect per capita health spending to increase fastest in upper-middle-income countries, at 5.3% (UI 4.1-6.8) per year. This growth is driven by continued growth in GDP, government spending, and government health spending. Lower-middle income countries are expected to grow at 4.2% (3.8-4.9). High-income countries are expected to grow at 2.1% (UI 1.8-2.4) and low-income countries are expected to grow at 1.8% (1.0-2.8). Despite this growth, health spending per capita in low-income countries is expected to remain low, at $154 (UI 133-181) per capita in 2030 and$195 (157-258) per capita in 2040. Increases in national health spending to reach the level of the countries who spend the most on health, relative to their level of economic development, would mean $321 (157-258) per capita was available for health in 2040 in low-income countries. Interpretation: Health spending is associated with economic development but past trends and relationships suggest that spending will remain variable, and low in some low-resource settings. Policy change could lead to increased health spending, although for the poorest countries external support might remain essential