Formative research for an mHealth program to improve the HIV care continuum in South Africa

ABSTRACT

In South Africa, high attrition rates throughout the care continuum present major barriers to controlling the HIV epidemic. Mobile health (mHealth) interventions may provide innovative opportunities for efficient healthcare delivery and improving retention in care. In this formative research, we interviewed 11 patients and 28 healthcare providers in North West Province, South Africa, to identify perceived benefits, concerns and suggestions for a future mHealth program to deliver HIV Viral Load and CD4 Count test results directly to patients via mobile phone. Thematic analysis found that reduced workload for providers, reduced wait times for patients, potential expanded uses and patient empowerment were the main perceived benefits of an mHealth program. Perceived concerns included privacy, disseminating distressing results through text messages and patients’ inability to interpret results. Participants felt that an mHealth program should complement face-to-face interactions and educational information to interpret results is needed. Providers identified logistical considerations and suggested protocols be developed. An mHealth program to deliver HIV test results directly to patients could mitigate multiple barriers to care but needs to be tested for efficacy. Concerns identified by patients and providers must be addressed in designing the program to successfully integrate with health facility workflow and ensure its sustainability.     

Hepatitis C Virus Genotype 4 Resistance and Subtype Demographic Characterization of Patients Treated with Ombitasvir plus Paritaprevir/Ritonavir

Hepatitis C virus (HCV) genotype 4 (GT4) is genetically diverse, with 17 confirmed subtypes, and comprises approximately 13% of infections worldwide. In this study, we identified GT4 subtypes by phylogenetic analysis, assessed differences in patient demographics across GT4 subtypes, examined baseline sequence variability among subtypes and the potential impact on treatment outcome, and analyzed the development of viral resistance in patients who received a regimen of ombitasvir (nonstructural protein 5A [NS5A] inhibitor) plus ritonavir-boosted paritaprevir (NS3/4A inhibitor) with or without ribavirin (RBV) for the treatment of HCV GT4 infection. Phylogenetic analysis of HCV NS3/4A, NS5A, and NS5B nucleotide sequences identified 7 subtypes (4a, 4b, 4c, 4d, 4f, 4g/4k, and 4o) among 132 patient samples. Subtype prevalence varied by country, and the distributions of patient birth cohort and race were significantly different across GT4 subtypes 4a, 4d, and non-4a/4d. Baseline amino acid variability was detected in NS5A across GT4 subtypes but had no impact on treatment outcome. Three patients experienced virologic failure and were infected with subtype 4d, and the predominant resistance-associated variants at the time of failure were D168V in NS3 and L28V in NS5A. Overall, high response rates were observed among patients infected with 7 HCV GT4 subtypes, with no impact of baseline variants on treatment outcome. GT4 subtype distribution in this study differed based on patient demographics and geography.     

Larvicidal and pupicidal activities of ecbolin A and ecbolin B isolated from Ecbolium viride (Forssk.) Alston against Culex quinquefasciatus Say (Diptera: Culicidae)

The mosquitocidal activity of different fractions and isolated compounds from the ethyl acetate extract of Ecbolium viride root was assessed on larvae and pupae of Culex quinquefasciatus Say (Diptera: Culicidae). The larvae and pupae were exposed to concentrations of 6.125, 12.5, 25 and 50 ppm for fractions and 1, 2.5, 5 and 10 ppm for compound. Among the 12 fractions screened, fraction 6 from the ethyl acetate extract of E. viride was recorded to have the highest larvicidal and pupicidal activities against C. quinquefasciatus. The lethal concentration (LC₅₀ and LC₉₀) values of fraction 6 were 4.26 and 9.0 ppm against C. quinquefasciatus larvae and 6.55 and 12.19 ppm against C. quinquefasciatus pupae, respectively, in 24 h. Fraction 7 was recorded to have moderate activity with LC₅₀ and LC₉₀ values of 11.25 and 25.02 ppm against C. quinquefasciatus larvae and 13.33 and 31.15 ppm against C. quinquefasciatus pupae, respectively, in 24 h. Ecbolin A and ecbolin B were identified from fractions 7 and 6, respectively. The structure of the isolated compounds was identified on the basis of spectral data (¹H NMR and ¹³C NMR) and compared with literature spectral data. Further, the isolated compound, ecbolin B, from fraction 6 was recorded to have strong larvicidal and pupicidal activities than ecbolin A. The LC₅₀ and LC₉₀ values of ecbolin B on C. quinquefasciatus larvae were 1.36 and 2.76 ppm, and on pupae, these were 1.54 and 3.51 ppm, respectively. The present results suggest that ecbolin B could be used as a mosquitocidal agent against C. quinquefasciatus.     

Acute ammonium dichromate poisoning in a 2 year-old child

Hexavalent chromium compounds are most commonly used in printing, dyeing, plastics and rayon manufacturing. Poisoning in children by ammonium dichromate, an odorless and bright orange-red crystal, are rarely reported. Acute poisoning will result in death due to multi-organ failure. The target organs that are affected by this poison are the respiratory system, kidneys, liver, eyes and skin. On ingestion, initially there is a relative lack of severe symptoms and signs. Hence, the delay in seeking medical attention could lead to the increased rate of mortality. In this case study, we report the ingestion of ammonium dichromate by a child. Despite appropriate management, such as hepatic supportive measures and plasma transfusion, the toxicity progressed to multi-organ failure and death.     

Oesophageal atresia: The growth gap

Poor growth is an under-recognised yet significant long-term sequelae of oesophageal atresia(OA) repair. Few studies have specifically explored the reasons for growth impairment in this complex cohort. The association between poor growth with younger age and fundoplication appears to have the strongest supportive evidence, highlighting the need for early involvement of a dietitian and speech pathologist, and consideration of optimal medical reflux management prior to referring for anti-reflux surgery. However, it remains difficult to reach conclusions regarding other factors which may negatively influence growth, due to conflicting findings, inconsistent definitions and lack of validated tool utilisation. While swallowing and feeding difficulties are particularly frequent in younger children, their relationship with growth remains unclear. It is possible that these morbidities impact on the diet of children with OA, but detailed analysis of dietary composition and quality, and its relationship with these complications and growth, has not yet been conducted. Another potential area of research in OA is the role of the microbiota in growth and nutrition. While the microbiota has been linked to growth impairment in other paediatric conditions,it is yet to be investigated in OA. Further research is needed to identify the most,important contributory factors to poor growth, the role of the intestinal microbiota, and effective interventions to maximise growth and nutritional outcomes in this cohort.     

Hammock mitral valve: A rare cause of congenital mitral regurgitation – A case report

Hammock valve, also known as anomalous mitral arcade is a rare mechanism for congenital mitral insufficiency. We report a case of a two-week-old neonate who presented with features of heart failure and an apical systolic murmur. Echocardiogram showed severe mitral regurgitation and abnormal mitral valve with direct attachment of mitral leaflets to papillary muscle without intervening chordae tendinae, typical of hammock valve. Heart failure was controlled with ionotrpes and diuretics. The literature on the hammock mitral valve is reviewed.     

Conserved features of intermediates in amyloid assembly determine their benign or toxic states

Some amyloid-forming polypeptides are associated with devastating human diseases and others provide important biological functions. For both, oligomeric intermediates appear during amyloid assembly. Currently we have few tools for characterizing these conformationally labile intermediates and discerning what governs their benign versus toxic states. Here, we examine intermediates in the assembly of a normal, functional amyloid, the prion-determining region of yeast Sup35 (NM). During assembly, NM formed a variety of oligomers with different sizes and conformation-specific antibody reactivities. Earlier oligomers were less compact and reacted with the conformational antibody A11. More mature oligomers were more compact and reacted with conformational antibody OC. We found we could arrest NM in either of these two distinct oligomeric states with small molecules or crosslinking. The A11-reactive oligomers were more hydrophobic (as measured by Nile Red binding) and were highly toxic to neuronal cells, while OC-reactive oligomers were less hydrophobic and were not toxic. The A11 and OC antibodies were originally raised against oligomers of Aβ, an amyloidogenic peptide implicated in Alzheimer's disease (AD) that is completely unrelated to NM in sequence. Thus, this natural yeast prion samples two conformational states similar to those sampled by Aβ, and when assembly stalls at one of these two states, but not the other, it becomes extremely toxic. Our results have implications for selective pressures operating on the evolution of amyloid folds across a billion years of evolution. Understanding the features that govern such conformational transitions will shed light on human disease and evolution alike.     

A role for dynamin in triggering ethanol tolerance

Background: A prevailing hypothesis is that the set of genes that underlie the endophenotypes of alcoholism overlap with those responsible for the addicted state. Functional ethanol tolerance, an endophenotype of alcoholism, is defined as a reduced response to ethanol caused by prior ethanol exposure. The neuronal origins of functional rapid tolerance are thought to be a homeostatic response of the nervous system that counters the effects of the drug. Synaptic proteins that regulate neuronal activity are an important evolutionarily conserved target of ethanol. Methods: We used mutant analysis in Drosophila to identify synaptic proteins that are important for the acquisition of rapid tolerance to sedation with ethanol. Tolerance was assayed by sedating flies with ethanol vapor and comparing the recovery time of flies after their first sedation and their second sedation. Temperature‐sensitive paralytic mutants that alter key facets of synaptic neurotransmission, such as the propagation of action potentials, synaptic vesicle fusion, exocytosis, and endocytosis, were tested for the ability to acquire functional tolerance at both the permissive and restrictive temperatures. Results: The shibire gene encodes Drosophila Dynamin. We tested 2 temperature‐sensitive alleles of the gene. The shi^ts1 allele blocked tolerance at both the permissive and restrictive temperatures, while shi^ts2 blocked only at the restrictive temperature. Using the temperature‐sensitive property of shi^ts2, we showed that Dynamin function is required concomitant with exposure to ethanol. A temperature‐sensitive allele of the Syntaxin 1A gene, Syx1A^3–69, also blocked the acquisition of ethanol tolerance. Conclusions: We have shown that shibire and Syntaxin 1A are required for the acquisition of rapid functional tolerance to ethanol. Furthermore, the shibire gene product, Dynamin, appears to be required for an immediate early response to ethanol that triggers a cellular response leading to rapid functional tolerance.