Cascaded clinical mentoring improves health workers selfefficacy in provision of integrated HIV care in rural hospitals in Kenya

Objective: To evaluate cascaded clinical mentorship strategy on access and health-worker’s self-efficacy in delivery of integrated HIV services. Design: A cross sectional survey study design. Setting: Government health facilities in the Coastal region and City of Nairobi, Kenya. Participants: Nurses and clinical officers who were recipients of cascaded mentorship. Intervention: Training of volunteer health-workers on mentorship and the HIV care package by a team of master mentors followed by support to carry out mentorship among fellow health-workers. Outcome measure: Access to HIV services, and health-worker self-reported efficacy in delivering integrated HIV care services based on an anonymous standard self-administered tool that evaluated 9 domains of HIV care. Results: There was an exponential increase in mentorship services, 126 volunteer health-workers were trained, and they formed 22 multidisciplinary District teams who extended mentorship to 231 health facilities. In the 33 months a total of 5503 mentor visits and 7724 mentoring sessions were made. The evaluated 150 health workers self-reported significant improvement in all 9 domains of HIV care compared to baseline (p < 0.001). Health-workers were exposed to a mean of 6 mentor-ship sessions. On controlling for region and cadre of staff, number of mentor-ship sessions were significantly associated with increased competence in 7 of 9 fields (p< 0.01). Compared to volunteer mentors, mentorship and site visits by master mentors were five and twice more costly respectively. Conclusions: Cascaded HIV mentorship increased staff self-efficacy and access to HIV treatment services. The impact of this cascaded mentorship on patient outcomes should be evaluated

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Recombinant Rhipicephalus appendiculatus gut (Ra86) and salivary gland cement (Trp64) proteins as candidate antigens for inclusion in tick vaccines: protective effetcs of Ra86 on infestation with adult R. appendiculatus.

Rhipicephalus appendiculatus gut protein Ra86 (variants Ra85A and Ra92A) and the salivary gland cement protein (Trp64) were expressed in the baculovirus-insect cell system. The recombinant gut proteins expressed as soluble proteins and the recombinant cement protein, as insoluble inclusion bodies, were used to immunize rabbits, which were then challenged with larval, nymphal, and adult stages of R. appendiculatus ticks. High tick mortality (23.3%) occurred on adult ticks that fed on rabbits vaccinated with the gut proteins, compared with 1.9% mortality in ticks that fed on unvaccinated naïve control rabbits. The mean weight of engorged female ticks was significantly reduced by 31.5% in rabbits vaccinated with the Ra86 recombinant protein compared with controls, as was egg production. Marked effects on these parameters were also observed in adult ticks as a result from vaccination using Trp64, but these were not statistically significant. For both antigens, there was no demonstrable effect on larval or nymphal ticks. This study demonstrates for the first time the protective efficacy of a homolog of Boophilus microplus Bm86 in reducing tick infestation by the adult stage of the three-host tick R. appendiculatus. The results demonstrate the potential of Ra86 for vaccine development against this tick and for the control of East Coast fever