Cardiac ultrasound in resource-limited settings (CURLS): towards a wider use of basic echo applications in Africa

Background: Point-of-care ultrasound is increasingly being used as a diagnostic tool in resource-limited settings. The majority of existing ultrasound protocols have been developed and implemented in high-resource settings. In sub-Saharan Africa (SSA), patients with heart failure of various etiologies commonly present late in the disease process, with a similar syndrome of dyspnea, edema and cardiomegaly on chest X-ray. The causes of heart failure in SSA differ from those in high-resource settings. Point-of-care ultrasound has the potential to identify the underlying etiology of heart failure, and lead to targeted therapy. Based on a literature review and weighted score of disease prevalence, diagnostic impact and difficulty in performing the ultrasound, we propose a context-specific cardiac ultrasound protocol to help differentiate patients presenting with heart failure in SSA. Results: Pericardial effusion, dilated cardiomyopathy, cor pulmonale, mitral valve disease, and left ventricular hypertrophy were identified as target conditions for a focused ultrasound protocol in patients with cardiac failure and cardiomegaly in SSA. By utilizing a simplified 5-question approach with all images obtained from the subxiphoid view, the protocol is suitable for use by health care professionals with limited ultrasound experience. Conclusions: The “Cardiac ultrasound for resource-limited settings (CURLS)” protocol is a context-specific algorithm designed to aid the clinician in diagnosing the five most clinically relevant etiologies of heart failure and cardiomegaly in SSA. The protocol has the potential to influence treatment decisi

Effectiveness of service models and organisational structures supporting tuberculosis identification and management in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review

OBJECTIVE: To determine which service models and organisational structures are effective and cost-effective for delivering tuberculosis (TB) services to hard-to-reach populations. DESIGN: Embase and MEDLINE (1990–2017) were searched in order to update and extend the 2011 systematic review commissioned by National Institute for Health and Care Excellence (NICE), discussing interventions targeting service models and organisational structures for the identification and management of TB in hard-to-reach populations. The NICE and Cochrane Collaboration standards were followed. SETTING: European Union, European Economic Area, European Union candidate countries and Organisation for Economic Co-operation and Development countries. PARTICIPANTS: Hard-to-reach populations, including migrants, homeless people, drug users, prisoners, sex workers, people living with HIV and children within vulnerable and hard-to-reach populations. PRIMARY AND SECONDARY OUTCOME MEASURES: Effectiveness and cost-effectiveness of the interventions. RESULTS: From the 19 720 citations found, five new studies were identified, in addition to the six discussed in the NICE review. Community health workers from the same migrant community, street teams and peers improved TB screening uptake by providing health education, promoting TB screening and organising contact tracing. Mobile TB clinics, specialised TB clinics and improved cooperation between healthcare services can be effective at identifying and treating active TB cases and are likely to be cost-effective. No difference in treatment outcome was detected when directly observed therapy was delivered at a health clinic or at a convenient location in the community. CONLCUSIONS: Although evidence is limited due to the lack of high-quality studies, interventions using peers and community health workers, mobile TB services, specialised TB clinics and improved cooperation between health services can be effective to control TB in hard-to-reach populations. Future studies should evaluate the (cost-)effectiveness of interventions on TB identification and management in hard-to-reach populations and countries should be urged to publish the outcomes of their TB control systems

The Compartmentalisation of Phosphorylated Free Oligosaccharides in Cells from a CDG Ig Patient Reveals a Novel ER-to-Cytosol Translocation Process

BACKGROUND: Biosynthesis of the dolichol linked oligosaccharide (DLO) required for protein N-glycosylation starts on the cytoplasmic face of the ER to give Man(5)GlcNAc(2)-PP-dolichol, which then flips into the ER for further glycosylation yielding mature DLO (Glc(3)Man(9)GlcNAc(2)-PP-dolichol). After transfer of Glc(3)Man(9)GlcNAc(2) onto protein, dolichol-PP is recycled to dolichol-P and reused for DLO biosynthesis. Because de novo dolichol synthesis is slow, dolichol recycling is rate limiting for protein glycosylation. Immature DLO intermediates may also be recycled by pyrophosphatase-mediated cleavage to yield dolichol-P and phosphorylated oligosaccharides (fOSGN2-P). Here, we examine fOSGN2-P generation in cells from patients with type I Congenital Disorders of Glycosylation (CDG I) in which defects in the dolichol cycle cause accumulation of immature DLO intermediates and protein hypoglycosylation. METHODS AND PRINCIPAL FINDINGS: In EBV-transformed lymphoblastoid cells from CDG I patients and normal subjects a correlation exists between the quantities of metabolically radiolabeled fOSGN2-P and truncated DLO intermediates only when these two classes of compounds possess 7 or less hexose residues. Larger fOSGN2-P were difficult to detect despite an abundance of more fully mannosylated and glucosylated DLO. When CDG Ig cells, which accumulate Man(7)GlcNAc(2)-PP-dolichol, are permeabilised so that vesicular transport and protein synthesis are abolished, the DLO pool required for Man(7)GlcNAc(2)-P generation could be depleted by adding exogenous glycosylation acceptor peptide. Under conditions where a glycotripeptide and neutral free oligosaccharides remain predominantly in the lumen of the ER, Man(7)GlcNAc(2)-P appears in the cytosol without detectable generation of ER luminal Man(7)GlcNAc(2)-P. CONCLUSIONS AND SIGNIFICANCE: The DLO pools required for N-glycosylation and fOSGN2-P generation are functionally linked and this substantiates the hypothesis that pyrophosphatase-mediated cleavage of DLO intermediates yields recyclable dolichol-P. The kinetics of cytosolic fOSGN2-P generation from a luminally-generated DLO intermediate demonstrate the presence of a previously undetected ER-to-cytosol translocation process for either fOSGN2-P or DLO

Designing antifilarial drug trials using clinical trial simulators

Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles

TB and HIV in the Central African region: current knowledge and knowledge gaps

Purpose Reliable and comprehensive data on the HIV/AIDS and TB co-pandemics from Central Africa remain scarce. This systematic review provides a comprehensive overview on current and past research activities in the region and provides a basis for future research work to close knowledge gaps. Methods The scientific literature was searched for publications meeting the following search terms: ``tuberculosis'' or ``HIV'' or ``acquired immunodeficiency syndrome'', combined with ``Central Africa'', or the names of individual countries within the region. Original studies, reviews and case series were included, and a selection of relevant articles was made. Results Most research in the field of HIV and TB has been conducted in Cameroon, where the epidemics have been described fairly well. The Democratic Republic of Congo ranked second on the amount of publications, despite the civil wars over the past several decades. Very little has been published on HIV and TB in the other countries, possibly due to the poor infrastructure of health care systems, lack of scientific capacity building or shortage of laboratory equipment. Conclusions Despite the relatively high burden of HIV and TB in the Central African region, the amount of research activities on these topics is limited. A better understanding of the co-epidemics in this region is urgently needed. The occurrence of opportunistic infections, treatment complications and drug resistance in TB and HIV need to be better described; the failure of public health systems needs to be understood, and research infrastructure needs to be developed. Only then will it be possible to turn the tide against the HIV and TB epidemics in this region